Cooperative Roles of Nectins with Cadherins in Physiological and Pathological Processes

  • Takeshi Fujiwara
  • Akira Mizoguchi
  • Yoshimi TakaiEmail author


Mammalian tissues and organs are composed of cells of different types and these cells adhere to one another to form societies of cells including the mesenchyme and the epithelium. Cell–cell adhesion in the mesenchyme is weak whereas cells are organized into closely adherent barrier-forming sheets by cell–cell adhesions in the epithelium. Cell–cell adhesion is organized to allow the release or incorporation of individual cells during various physiological or pathological processes, for example, organ development and growth, maintenance and repair of tissues, or tumorigenesis. One prominent cell–cell adhesion apparatus is adherens junctions (AJs). The central structural components of AJs are transmembrane cell–cell adhesion molecules, cadherins and nectins. Nectins recruit cadherins to the cell–cell contact sites and mediate cell–cell adhesions that control local membrane dynamics for cell polarization and coordinate shape change at the cellular level. Nectins are engaged in calcium-independent homophilic and heterophilic trans-interactions between opposing cells in numerous tissues and cell types to form homotypic and heterotypic cell–cell adhesion, whereas cadherins are primarily involved in calcium-dependent homophilic trans-interactions between opposing cells to form homotypic cell–cell adhesion. Nectins function cooperatively with or independently of cadherins to control physiological processes and cooperative ones include the formation of AJs and apico-basal polarity, apical constriction, contact inhibition of cell movement and proliferation, formation of synapse, formation of checkerboard-like cell arrangement, ciliary epithelium and lens, and neuronal cell adhesion and migration. Moreover, nectins are involved in pathological processes including virus infection and human inherited disorder.


Nectin Cadherin Afadin Cell adhesion Cell polarity Synapse formation Apical constriction Cell migration Disease 



We thank our colleagues and collaborators for their enormous contributions and outstanding achievements, Drs. Kenji Mandai, Yoshiyuki Rikitake, Kiyohito Mizutani, and Tomohiko Maruo for their helpful advice and discussions. This work was supported by Grants-in-Aid for Scientific Research (S) (21227005 to Y.T.) and (B) (23300284 to A.M.) from the Japan Society for the Promotion of Science and Grant-in-Aid for Scientific Research on Innovative Areas (26114007 to Y.T.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.


  1. Adachi M, Hamazaki Y, Kobayashi Y et al (2009) Similar and distinct properties of MUPP1 and Patj, two homologous PDZ domain-containing tight-junction proteins. Mol Cell Biol 29:2372–2389PubMedPubMedCentralCrossRefGoogle Scholar
  2. Amano H, Ikeda W, Kawano S et al (2008) Interaction and localization of Necl-5 and PDGF receptor beta at the leading edges of moving NIH3T3 cells: Implications for directional cell movement. Genes Cells 13:269–284PubMedCrossRefGoogle Scholar
  3. Amaral DG, Dent JA (1981) Development of the mossy fibers of the dentate gyrus: I. A light and electron microscopic study of the mossy fibers and their expansions. J Comp Neurol 195:51–86PubMedCrossRefGoogle Scholar
  4. Asada M, Irie K, Morimoto K et al (2003) ADIP, a novel Afadin- and alpha-actinin-binding protein localized at cell-cell adherens junctions. J Biol Chem 278:4103–4111PubMedCrossRefGoogle Scholar
  5. Asakura T, Nakanishi H, Sakisaka T et al (1999) Similar and differential behaviour between the nectin-afadin-ponsin and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells. Genes Cells 4:573–581PubMedCrossRefGoogle Scholar
  6. Athanassiadou AM, Patsouris E, Tsipis A et al (2011) The significance of Survivin and Nectin-4 expression in the prognosis of breast carcinoma. Folia Histochem Cytobiol 49:26–33PubMedCrossRefGoogle Scholar
  7. Ballester M, Gonin J, Rodenas A et al (2012) Eutopic endometrium and peritoneal, ovarian and colorectal endometriotic tissues express a different profile of nectin-1, -3, -4 and nectin-like molecule 2. Hum Reprod 27:3179–3186PubMedCrossRefGoogle Scholar
  8. Barrett K, Leptin M, Settleman J (1997) The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation. Cell 91:905–915PubMedCrossRefGoogle Scholar
  9. Barron MJ, Brookes SJ, Draper CE et al (2008) The cell adhesion molecule nectin-1 is critical for normal enamel formation in mice. Hum Mol Genet 17:3509–3520PubMedPubMedCentralCrossRefGoogle Scholar
  10. Beaudoin GM 3rd, Schofield CM, Nuwal T et al (2012) Afadin, a Ras/Rap effector that controls cadherin function, promotes spine and excitatory synapse density in the hippocampus. J Neurosci 32:99–110PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bermejo E, Martinez-Frias ML (1998) Congenital eye malformations: clinical-epidemiological analysis of 1,124,654 consecutive births in Spain. Am J Med Genet 75:497–504PubMedCrossRefGoogle Scholar
  12. Birch J, Juleff N, Heaton MP et al (2013) Characterization of ovine Nectin-4, a novel peste des petits ruminants virus receptor. J Virol 87:4756–4761PubMedPubMedCentralCrossRefGoogle Scholar
  13. Bottino C, Castriconi R, Pende D et al (2003) Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med 198:557–567PubMedPubMedCentralCrossRefGoogle Scholar
  14. Brancati F, Fortugno P, Bottillo I et al (2010) Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome. Am J Hum Genet 87:265–273PubMedPubMedCentralCrossRefGoogle Scholar
  15. Cain S, Martinez G, Kokkinos MI et al (2008) Differential requirement for β-catenin in epithelial and fiber cells during lens development. Dev Biol 321:420–433PubMedCrossRefGoogle Scholar
  16. Choi YS, Gumbiner B (1989) Expression of cell adhesion molecule E-cadherin in Xenopus embryos begins at gastrulation and predominates in the ectoderm. J Cell Biol 108:2449–2458PubMedCrossRefGoogle Scholar
  17. Chow RL, Lang RA (2001) Early eye development in vertebrates. Annu Rev Cell Dev Biol 17:255–296PubMedCrossRefGoogle Scholar
  18. Christofori G (2003) Split personalities: the agonistic antagonist Sprouty. Nat Cell Biol 5:377–379PubMedCrossRefGoogle Scholar
  19. Colas JF, Schoenwolf GC (2001) Towards a cellular and molecular understanding of neurulation. Dev Dyn 221:117–145PubMedCrossRefGoogle Scholar
  20. Davidson LA, Keller RE (1999) Neural tube closure in Xenopus laevis involves medial migration, directed protrusive activity, cell intercalation and convergent extension. Development 126:4547–4556PubMedGoogle Scholar
  21. Dawes-Hoang RE, Parmar KM, Christiansen AE et al (2005) folded gastrulation, cell shape change and the control of myosin localization. Development 132:4165–4178PubMedCrossRefGoogle Scholar
  22. de Kloet ER, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6:463–475PubMedCrossRefGoogle Scholar
  23. Derycke MS, Pambuccian SE, Gilks CB et al (2010) Nectin 4 overexpression in ovarian cancer tissues and serum: potential role as a serum biomarker. Am J Clin Pathol 134:835–845PubMedPubMedCentralCrossRefGoogle Scholar
  24. Detrick RJ, Dickey D, Kintner CR (1990) The effects of N-cadherin misexpression on morphogenesis in Xenopus embryos. Neuron 4:493–506PubMedCrossRefGoogle Scholar
  25. Devilard E, Xerri L, Dubreuil P et al (2013) Nectin-3 (CD113) interacts with Nectin-2 (CD112) to promote lymphocyte transendothelial migration. PLoS One 8:e77424PubMedPubMedCentralCrossRefGoogle Scholar
  26. Dudak A, Kim J, Cheong B et al (2011) Membrane palmitoylated proteins regulate trafficking and processing of nectins. Eur J Cell Biol 90:365–375PubMedPubMedCentralCrossRefGoogle Scholar
  27. Eberle F, Dubreuil P, Mattei MG et al (1995) The human PRR2 gene, related to the human poliovirus receptor gene (PVR), is the true homolog of the murine MPH gene. Gene 159:267–272PubMedCrossRefGoogle Scholar
  28. Fabre-Lafay S, Garrido-Urbani S, Reymond N et al (2005) Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM-17. J Biol Chem 280:19543–19550PubMedCrossRefGoogle Scholar
  29. Fairbank PD, Lee C, Ellis A et al (2006) Shroom2 (APXL) regulates melanosome biogenesis and localization in the retinal pigment epithelium. Development 133:4109–4118PubMedCrossRefGoogle Scholar
  30. Fantin M, van der Kooij MA, Grosse J et al (2013) A key role for nectin-1 in the ventral hippocampus in contextual fear memory. PLoS One 8:e56897PubMedPubMedCentralCrossRefGoogle Scholar
  31. Fortugno P, Josselin E, Tsiakas K et al (2014) Nectin-4 mutations causing ectodermal dysplasia with syndactyly perturb the rac1 pathway and the kinetics of adherens junction formation. J Invest Dermatol 134:2146–2153PubMedCrossRefGoogle Scholar
  32. Fournier G, Cabaud O, Josselin E et al (2011) Loss of Af6/afadin, a marker of poor outcome in breast cancer, induces cell migration, invasiveness and tumor growth. Oncogene 30:3862–3874PubMedCrossRefGoogle Scholar
  33. Franco SJ, Martinez-Garay I, Gil-Sanz C et al (2011) Reelin regulates cadherin function via Dab1/Rap1 to control neuronal migration and lamination in the neocortex. Neuron 69:482–497PubMedPubMedCentralCrossRefGoogle Scholar
  34. Fujimori T, Miyatani S, Takeichi M (1990) Ectopic expression of N-cadherin perturbs histogenesis in Xenopus embryos. Development 110:97–104PubMedGoogle Scholar
  35. Fujito T, Ikeda W, Kakunaga S et al (2005) Inhibition of cell movement and proliferation by cell-cell contact-induced interaction of Necl-5 and nectin-3. J Cell Biol 171:165–173PubMedPubMedCentralCrossRefGoogle Scholar
  36. Fujiwara Y, Goda N, Tamashiro T et al (2015) Crystal structure of afadin PDZ domain–nectin-3 complex shows the structural plasticity of the ligand-binding site. Protein Sci 24:376–385PubMedPubMedCentralCrossRefGoogle Scholar
  37. Fukuda T, Kominami K, Wang S et al (2014) Aberrant cochlear hair cell attachments caused by Nectin-3 deficiency result in hair bundle abnormalities. Development 141:399–409PubMedCrossRefGoogle Scholar
  38. Fukuhara A, Shimizu K, Kawakatsu T et al (2003) Involvement of nectin-activated Cdc42 small G protein in organization of adherens and tight junctions in Madin-Darby canine kidney cells. J Biol Chem 278:51885–51893PubMedCrossRefGoogle Scholar
  39. Garcia R, Tocco G, Baudry M et al (1998) Exposure to a conditioned aversive environment interferes with long-term potentiation induction in the fimbria-CA3 pathway. Neuroscience 82:139–145PubMedCrossRefGoogle Scholar
  40. Geraghty RJ, Krummenacher C, Cohen GH et al (1998) Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science 280:1618–1620PubMedCrossRefGoogle Scholar
  41. Gil-Sanz C, Franco SJ, Martinez-Garay I et al (2013) Cajal-Retzius cells instruct neuronal migration by coincidence signaling between secreted and contact-dependent guidance cues. Neuron 79:461–477PubMedPubMedCentralCrossRefGoogle Scholar
  42. Gil-Sanz C, Landeira B, Ramos C et al (2014) Proliferative defects and formation of a double cortex in mice lacking Mltt4 and Cdh2 in the dorsal telencephalon. J Neurosci 34:10475–10487PubMedPubMedCentralCrossRefGoogle Scholar
  43. Ginsberg D, DeSimone D, Geiger B (1991) Expression of a novel cadherin (EP-cadherin) in unfertilized eggs and early Xenopus embryos. Development 111:315–325PubMedGoogle Scholar
  44. Goodrich LV, Strutt D (2011) Principles of planar polarity in animal development. Development 138:1877–1892PubMedPubMedCentralCrossRefGoogle Scholar
  45. Graw J (2009) Mouse models of cataract. J Genet 88:469–486PubMedCrossRefGoogle Scholar
  46. Gray RS, Roszko I, Solnica-Krezel L (2011) Planar cell polarity: coordinating morphogenetic cell behaviors with embryonic polarity. Dev Cell 21:120–133PubMedPubMedCentralCrossRefGoogle Scholar
  47. Gregory Call S, Brereton D, Bullard JT et al (2011) A zyxin-nectin interaction facilitates zyxin localization to cell-cell adhesions. Biochem Biophys Res Commun 415:485–489PubMedCrossRefGoogle Scholar
  48. Guzman G, Oh S, Shukla D et al (2006) Nectin-1 expression in the normal and neoplastic human uterine cervix. Arch Pathol Lab Med 130:1193–1195PubMedGoogle Scholar
  49. Häcker U, Perrimon ND (1998) RhoGEF2 encodes a member of the Dbl family of oncogenes and controls cell shape changes during gastrulation in Drosophila. Genes Dev 12:274–284PubMedPubMedCentralCrossRefGoogle Scholar
  50. Haigo SL, Hildebrand JD, Harland RM et al (2003) Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. Curr Biol 13:2125–2137PubMedCrossRefGoogle Scholar
  51. Harold D, Abraham R, Hollingworth P et al (2009) Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet 41:1088–1093PubMedPubMedCentralCrossRefGoogle Scholar
  52. Harrison OJ, Vendome J, Brasch J et al (2012) Nectin ectodomain structures reveal a canonical adhesive interface. Nat Struct Mol Biol 19:906–915PubMedPubMedCentralCrossRefGoogle Scholar
  53. Häussinger D, Ahrens T, Aberle T et al (2004) Proteolytic E-cadherin activation followed by solution NMR and X-ray crystallography. EMBO J 23:1699–1708PubMedPubMedCentralCrossRefGoogle Scholar
  54. Hejtmancik JF (2008) Congenital cataracts and their molecular genetics. Sem Cell Dev Biol 19:134–149CrossRefGoogle Scholar
  55. Hildebrand JD (2005) Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network. J Cell Sci 118:5191–5203PubMedCrossRefGoogle Scholar
  56. Hirota T, Irie K, Okamoto R et al (2005) Transcriptional activation of the mouse Necl-5/Tage4/PVR/CD155 gene by fibroblast growth factor or oncogenic Ras through the Raf-MEK-ERK-AP-1 pathway. Oncogene 24:2229–2235PubMedCrossRefGoogle Scholar
  57. Honda T, Sakisaka T, Yamada T et al (2006) Involvement of nectins in the formation of puncta adherentia junctions and the mossy fiber trajectory in the mouse hippocampus. Mol Cell Neurosci 31:315–325PubMedCrossRefGoogle Scholar
  58. Hoshino T, Sakisaka T, Baba T et al (2005) Regulation of E-cadherin endocytosis by nectin through afadin, Rap1, and p120ctn. J Biol Chem 280:24095–24103PubMedCrossRefGoogle Scholar
  59. Huang YY, Yu Z, Lin SF et al (2007) Nectin-1 is a marker of thyroid cancer sensitivity to herpes oncolytic therapy. J Clin Endocrinol Metab 92:1965–1970PubMedCrossRefGoogle Scholar
  60. Ikeda W, Nakanishi H, Miyoshi J et al (1999) Afadin: A key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis. J Cell Biol 146:1117–1132PubMedPubMedCentralCrossRefGoogle Scholar
  61. Ikeda W, Kakunaga S, Itoh S et al (2003) Tage4/Nectin-like molecule-5 heterophilically trans-interacts with cell adhesion molecule Nectin-3 and enhances cell migration. J Biol Chem 278:28167–28172PubMedCrossRefGoogle Scholar
  62. Ikeda W, Kakunaga S, Takekuni K et al (2004) Nectin-like molecule-5/Tage4 enhances cell migration in an integrin-dependent, Nectin-3-independent manner. J Biol Chem 279:18015–18025PubMedCrossRefGoogle Scholar
  63. Inagaki M, Irie K, Ishizaki H et al (2005) Roles of cell-adhesion molecules nectin 1 and nectin 3 in ciliary body development. Development 132:1525–1537PubMedCrossRefGoogle Scholar
  64. Inagaki M, Irie K, Ishizaki H et al (2006) Role of cell adhesion molecule nectin-3 in spermatid development. Genes Cells 11:1125–1132PubMedCrossRefGoogle Scholar
  65. Indra I, Hong S, Troyanovsky R et al (2013) The adherens junction: a mosaic of cadherin and nectin clusters bundled by actin filaments. J Invest Dermatol 133:2546–2554PubMedPubMedCentralCrossRefGoogle Scholar
  66. Indra I, Troyanovsky R, Troyanovsky S (2014) Afadin controls cadherin cluster stability using clathrin-independent mechanism. Tissue Barriers 2:e28687PubMedPubMedCentralCrossRefGoogle Scholar
  67. Inoue T, Fujiwara T, Rikitake Y et al (2015) Nectin-1 spots as a novel adhesion apparatus that tethers mitral cell lateral dendrites in a dendritic meshwork structure of the developing mouse olfactory bulb. J Comp Neurol 523:1824–1839PubMedCrossRefGoogle Scholar
  68. Irie K, Shimizu K, Sakisaka T et al (2004) Roles and modes of action of nectins in cell-cell adhesion. Semin Cell Dev Biol 15:643–656PubMedCrossRefGoogle Scholar
  69. Ishiuchi T, Takeichi M (2012) Nectins localize Willin to cell-cell junctions. Genes Cells 17:387–397PubMedCrossRefGoogle Scholar
  70. Iwasawa N, Negishi M, Oinuma I (2012) R-Ras controls axon branching through afadin in cortical neurons. Mol Biol Cell 23:2793–2804PubMedPubMedCentralCrossRefGoogle Scholar
  71. Izumi H, Hirabayashi K, Nakamura N et al (2015) Nectin expression in pancreatic adenocarcinoma: nectin-3 is associated with a poor prognosis. Surg Today 45:487–494PubMedPubMedCentralCrossRefGoogle Scholar
  72. Jelani M, Chishti MS, Ahmad W (2011) Mutation in PVRL4 gene encoding nectin-4 underlies ectodermal-dysplasia-syndactyly syndrome (EDSS1). J Hum Genet 56:352–357PubMedCrossRefGoogle Scholar
  73. Jensen S, Goldschmidt E (1971) Genetic counselling in sporadic cases of congenital cataract. Acta Ophthalmol (Copenh) 49:572–576CrossRefGoogle Scholar
  74. Jossin Y, Cooper JA (2011) Reelin, Rap1 and N-cadherin orient the migration of multipolar neurons in the developing neocortex. Nat Neurosci 14:697–703PubMedPubMedCentralCrossRefGoogle Scholar
  75. Kajita M, Ikeda W, Tamaru Y et al (2007) Regulation of platelet-derived growth factor-induced Ras signaling by poliovirus receptor Necl-5 and negative growth regulator Sprouty2. Genes Cell 12:345–357CrossRefGoogle Scholar
  76. Kakunaga S, Ikeda W, Shingai T et al (2004) Enhancement of serum- and platelet-derived growth factor-induced cell proliferation by Necl-5/Tage4/poliovirus receptor/CD155 through the Ras-Raf-MEK-ERK signaling. J Biol Chem 279:36419–36425PubMedCrossRefGoogle Scholar
  77. Kälin M, Cima I, Schiess R et al (2011) Novel prognostic markers in the serum of patients with castration-resistant prostate cancer derived from quantitative analysis of the pten conditional knockout mouse proteome. Eur Urol 60:1235–1243PubMedCrossRefGoogle Scholar
  78. Kawakatsu T, Shimizu K, Honda T et al (2002) Trans-interactions of nectins induce formation of filopodia and Lamellipodia through the respective activation of Cdc42 and Rac small G proteins. J Biol Chem 277:50749–50755PubMedCrossRefGoogle Scholar
  79. Kawakatsu T, Ogita H, Fukuhara T et al (2005) Vav2 as a Rac-GDP/GTP exchange factor responsible for the nectin-induced, c-Src- and Cdc42-mediated activation of Rac. J Biol Chem 280:4940–4947PubMedCrossRefGoogle Scholar
  80. Kawauchi T, Sekine K, Shikanai M et al (2010) Rab GTPases-dependent endocytic pathways regulate neuronal migration and maturation through N-cadherin trafficking. Neuron 67:588–602PubMedCrossRefGoogle Scholar
  81. Kelley MW (2006) Regulation of cell fate in the sensory epithelia of the inner ear. Nat Rev Neurosci 7:837–849PubMedCrossRefGoogle Scholar
  82. Kim HJ, Bar-Sagi D (2004) Modulation of signalling by Sprouty: a developing story. Nat Rev Mol Cell Biol 5:441–450PubMedCrossRefGoogle Scholar
  83. Kinugasa M, Amano H, Satomi-Kobayashi S et al (2012) Necl-5/poliovirus receptor interacts with VEGFR2 and regulates VEGF-induced angiogenesis. Circ Res 110:716–726PubMedCrossRefGoogle Scholar
  84. Kobayashi R, Kurita S, Miyata M et al (2014) s-Afadin binds more preferentially to the cell adhesion molecules nectins than l-afadin. Genes Cells 19:853–863PubMedCrossRefGoogle Scholar
  85. Koch AW, Pokutta S, Lustig A et al (1997) Calcium binding and homoassociation of E-cadherin domains. Biochemistry 36:7697–7705PubMedCrossRefGoogle Scholar
  86. Koike S, Horie H, Ise I et al (1990) The poliovirus receptor protein is produced both as membrane-bound and secreted forms. EMBO J 9:3217–3224PubMedPubMedCentralGoogle Scholar
  87. Komura H, Ogita H, Ikeda W et al (2008) Establishment of cell polarity by afadin during the formation of embryoid bodies. Genes Cells 13:79–90PubMedCrossRefGoogle Scholar
  88. Kurokawa Y, Honma K, Takemasa I et al (2006) Central genetic alterations common to all HCV-positive, HBV-positive and non-B, non-C hepatocellular carcinoma: a new approach to identify novel tumor markers. Int J Oncol 28:383–391PubMedGoogle Scholar
  89. Lachke SA, Higgins AW, Inagaki M et al (2012) The cell adhesion gene PVRL3 is associated with congenital ocular defects. Hum Genet 131:235–250PubMedPubMedCentralCrossRefGoogle Scholar
  90. Lecuit T, Lenne PF (2007) Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis. Nat Rev Mol Cell Biol 8:633–644PubMedCrossRefGoogle Scholar
  91. Lee C, Scherr HM, Wallingford JB (2007) Shroom family proteins regulate gamma-tubulin distribution and microtubule architecture during epithelial cell shape change. Development 134:1431–1441PubMedCrossRefGoogle Scholar
  92. Letessier A, Garrido-Urbani S, Ginestier C et al (2007) Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer. Oncogene 26:298–307PubMedCrossRefGoogle Scholar
  93. Levi G, Gumbiner B, Thiery JP (1991) The distribution of E-cadherin during Xenopus laevis development. Development 111:159–169PubMedGoogle Scholar
  94. Logue MW, Schu M, Vardarajan BN et al (2011) A comprehensive genetic association study of Alzheimer disease in African Americans. Arch Neurol 68:1569–1579PubMedPubMedCentralCrossRefGoogle Scholar
  95. Lopez M, Eberle F, Mattei MG et al (1995) Complementary DNA characterization and chromosomal localization of a human gene related to the poliovirus receptor-encoding gene. Gene 155:261–265PubMedCrossRefGoogle Scholar
  96. Lorger M, Moelling K (2006) Regulation of epithelial wound closure and intercellular adhesion by interaction of AF6 with actin cytoskeleton. J Cell Sci 119:3385–3398PubMedCrossRefGoogle Scholar
  97. Maddala R, Chauhan BK, Walker C et al (2011) Rac1 GTPase-deficient mouse lens exhibits defects in shape, suture formation, fiber cell migration and survival. Dev Biol 360:30–43PubMedPubMedCentralCrossRefGoogle Scholar
  98. Mandai K, Nakanishi H, Satoh A et al (1997) Afadin: A novel actin filament-binding protein with one PDZ domain localized at cadherin-based cell-to-cell adherens junction. J Cell Biol 139:517–528PubMedPubMedCentralCrossRefGoogle Scholar
  99. Mandai K, Nakanishi H, Satoh A et al (1999) Ponsin/SH3P12: an l-afadin- and vinculin-binding protein localized at cell-cell and cell-matrix adherens junctions. J Cell Biol 144:1001–1017PubMedPubMedCentralCrossRefGoogle Scholar
  100. Mandai K, Rikitake Y, Mori M et al (2015) Nectins and nectin-like molecules in development and disease. Curr Top Dev Biol 112:197–231PubMedCrossRefGoogle Scholar
  101. Maniwa Y, Nishio W, Okita Y et al (2012) Expression of nectin 3: Novel prognostic marker of lung adenocarcinoma. Thoracic Can 3:175–181CrossRefGoogle Scholar
  102. Martin TA, Lane J, Harrison GM et al (2013) The expression of the Nectin complex in human breast cancer and the role of Nectin-3 in the control of tight junctions during metastasis. PLoS One 8:e82696PubMedPubMedCentralCrossRefGoogle Scholar
  103. Martinez-Rico C, Pincet F, Perez E et al (2005) Separation force measurements reveal different types of modulation of E-cadherin-based adhesion by nectin-1 and -3. J Biol Chem 280:4753–4760PubMedCrossRefGoogle Scholar
  104. Martinez-Sanz E, Del Rio A, Barrio C et al (2008) Alteration of medial-edge epithelium cell adhesion in two Tgf-beta3 null mouse strains. Differentiation 76:417–430PubMedPubMedCentralCrossRefGoogle Scholar
  105. Matsushima H, Utani A, Endo H et al (2003) The expression of nectin-1alpha in normal human skin and various skin tumours. Br J Dermatol 148:755–762PubMedCrossRefGoogle Scholar
  106. Maurin H, Seymour CM, Lechat B et al (2013) Tauopathy differentially affects cell adhesion molecules in mouse brain: early down-regulation of nectin-3 in stratum lacunosum moleculare. PLoS One 8:e63589PubMedPubMedCentralCrossRefGoogle Scholar
  107. Mayor R, Carmona-Fontaine C (2010) Keeping in touch with contact inhibition of locomotion. Trends Cell Biol 20:319–328PubMedPubMedCentralCrossRefGoogle Scholar
  108. McAvoy JW (1980) Induction of the eye lens. Differentiation 17:137–149PubMedCrossRefGoogle Scholar
  109. McClatchey AI, Yap AS (2012) Contact inhibition (of proliferation) redux. Curr Opin Cell Biol 24:685–694PubMedCrossRefGoogle Scholar
  110. McEwen BS (2003) Mood disorders and allostatic load. Biol Psychiatry 54:200–207PubMedCrossRefGoogle Scholar
  111. McKenzie E, Krupin A, Kelley MW (2004) Cellular growth and rearrangement during the development of the mammalian organ of Corti. Dev Dyn 229:802–812PubMedCrossRefGoogle Scholar
  112. Mendelsohn CL, Wimmer E, Racaniello VR (1989) Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily. Cell 56:855–865PubMedCrossRefGoogle Scholar
  113. Miao X, Yang ZL, Xiong L et al (2013) Nectin-2 and DDX3 are biomarkers for metastasis and poor prognosis of squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder. Int J Clin Exp Pathol 6:179–190PubMedPubMedCentralGoogle Scholar
  114. Minami Y, Ikeda W, Kajita M et al (2007) Necl-5/poliovirus receptor interacts in cis with integrin alphaVbeta3 and regulates its clustering and focal complex formation. J Biol Chem 282:18481–18496PubMedCrossRefGoogle Scholar
  115. Minami A, Mizutani K, Waseda M et al (2010) Necl-5/PVR enhances PDGF-induced attraction of growing microtubules to the plasma membrane of the leading edge of moving NIH3T3 cells. Genes Cells 15:1123–1135PubMedCrossRefGoogle Scholar
  116. Miyahara M, Nakanishi H, Takahashi K et al (2000) Interaction of nectin with afadin is necessary for its clustering at cell-cell contact sites but not for its cis dimerization or trans interaction. J Biol Chem 275:613–618PubMedCrossRefGoogle Scholar
  117. Miyata M, Rikitake Y, Takahashi M et al (2009) Regulation by afadin of cyclical activation and inactivation of Rap1, Rac1, and RhoA small G proteins at leading edges of moving NIH3T3 cells. J Biol Chem 284:24595–24609PubMedPubMedCentralCrossRefGoogle Scholar
  118. Miyoshi J, Takai Y (2005) Molecular perspective on tight-junction assembly and epithelial polarity. Adv Drug Deliv Rev 57:815–855PubMedCrossRefGoogle Scholar
  119. Miyoshi J, Takai Y (2007) Nectin and nectin-like molecules: biology and pathology. Am J Nephrol 27:590–604PubMedCrossRefGoogle Scholar
  120. Mizoguchi A, Nakanishi H, Kimura K et al (2002) Nectin: an adhesion molecule involved in formation of synapses. J Cell Biol 156:555–565PubMedPubMedCentralCrossRefGoogle Scholar
  121. Montcouquiol M, Kelley MW (2003) Planar and vertical signals control cellular differentiation and patterning in the mammalian cochlea. J Neurosci 23:9469–9478PubMedGoogle Scholar
  122. Montcouquiol M, Rachel RA, Lanford PJ et al (2003) Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. Nature 423:173–177PubMedCrossRefGoogle Scholar
  123. Mori M, Rikitake Y, Mandai K et al (2014) Roles of nectins and nectin-like molecules in the nervous system. Adv Neurobiol 8:91–116PubMedCrossRefGoogle Scholar
  124. Morita H, Nandadasa S, Yamamoto TS et al (2010) Nectin-2 and N-cadherin interact through extracellular domains and induce apical accumulation of F-actin in apical constriction of Xenopus neural tube morphogenesis. Development 137:1315–1325PubMedPubMedCentralCrossRefGoogle Scholar
  125. Motanis H, Maroun M (2010) Exposure to a novel context following contextual fear conditioning enhances the induction of hippocampal long-term potentiation. Eur J Neurosci 32:840–846PubMedCrossRefGoogle Scholar
  126. Mueller S, Rosenquist TA, Takai Y et al (2003) Loss of nectin-2 at Sertoli-spermatid junctions leads to male infertility and correlates with severe spermatozoan head and midpiece malformation, impaired binding to the zona pellucida, and oocyte penetration. Biol Reprod 69:1330–1340PubMedCrossRefGoogle Scholar
  127. Muhlebach MD, Mateo M, Sinn PL et al (2011) Adherens junction protein nectin-4 is the epithelial receptor for measles virus. Nature 480:530–533PubMedPubMedCentralGoogle Scholar
  128. Nadarajah B, Brunstrom JE, Grutzendler J et al (2001) Two modes of radial migration in early development of the cerebral cortex. Nat Neurosci 4:143–150PubMedCrossRefGoogle Scholar
  129. Nakanishi H, Takai Y (2004) Roles of nectins in cell adhesion, migration and polarization. Biol Chem 385:885–892PubMedCrossRefGoogle Scholar
  130. Nandadasa S, Tao Q, Menon NR et al (2009) N- and E-cadherins in Xenopus are specifically required in the neural and non-neural ectoderm, respectively, for F-actin assembly and morphogenetic movements. Development 136:1327–1338PubMedPubMedCentralCrossRefGoogle Scholar
  131. Narita H, Yamamoto Y, Suzuki M et al (2011) Crystal Structure of the cis-Dimer of Nectin-1: implications for the architecture of cell-cell junctions. J Biol Chem 286:12659–12669PubMedPubMedCentralCrossRefGoogle Scholar
  132. Nejsum LN, Nelson WJ (2009) Epithelial cell surface polarity: the early steps. Front Biosci (Landmark Ed) 14:1088–1098CrossRefGoogle Scholar
  133. Nelson WJ, Nusse R (2004) Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303:1483–1487PubMedPubMedCentralCrossRefGoogle Scholar
  134. Niessen CM, Leckband D, Yap AS (2011) Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation. Physiol Rev 91:691–731PubMedPubMedCentralCrossRefGoogle Scholar
  135. Nishimura T, Takeichi M (2008) Shroom3-mediated recruitment of Rho kinases to the apical cell junctions regulates epithelial and neuroepithelial planar remodeling. Development 135:1493–1502PubMedCrossRefGoogle Scholar
  136. Nishiwada S, Sho M, Yasuda S et al (2015) Nectin-4 expression contributes to tumor proliferation, angiogenesis and patient prognosis in human pancreatic cancer. J Exp Clin Cancer Res 34:30PubMedPubMedCentralCrossRefGoogle Scholar
  137. Noren NK, Liu BP, Burridge K et al (2000) p120 catenin regulates the actin cytoskeleton via Rho family GTPases. J Cell Biol 150:567–580PubMedPubMedCentralCrossRefGoogle Scholar
  138. Noyce RS, Bondre DG, Ha MN et al (2011) Tumor cell marker PVRL4 (nectin 4) is an epithelial cell receptor for measles virus. PLoS Pathog 7:e1002240PubMedPubMedCentralCrossRefGoogle Scholar
  139. Noyce RS, Delpeut S, Richardson CD (2013) Dog nectin-4 is an epithelial cell receptor for canine distemper virus that facilitates virus entry and syncytia formation. Virology 436:210–220PubMedCrossRefGoogle Scholar
  140. Ogita H, Takai Y (2006) Nectins and nectin-like molecules: roles in cell adhesion, polarization, movement, and proliferation. IUBMB Life 58:334–343PubMedCrossRefGoogle Scholar
  141. Ogita H, Takai Y (2008) Cross-talk among integrin, cadherin, and growth factor receptor: roles of nectin and nectin-like molecule. Int Rev Cytol 265:1–54PubMedCrossRefGoogle Scholar
  142. Ogita H, Ikeda W, Takai Y (2008) Roles of cell adhesion molecules nectin and nectin-like molecule-5 in the regulation of cell movement and proliferation. J Microsc 231:455–465PubMedCrossRefGoogle Scholar
  143. Ogita H, Rikitake Y, Miyoshi J et al (2010) Cell adhesion molecules nectins and associating proteins: Implications for physiology and pathology. Proc Jpn Acad Ser B Phys Biol Sci 86:621–629PubMedPubMedCentralCrossRefGoogle Scholar
  144. Ohka S, Nihei C, Yamazaki M et al (2012) Poliovirus trafficking toward central nervous system via human poliovirus receptor-dependent and -independent pathway. Front Microbiol 3:147PubMedPubMedCentralCrossRefGoogle Scholar
  145. Okabe N, Ozaki-Kuroda K, Nakanishi H et al (2004a) Expression patterns of nectins and afadin during epithelial remodeling in the mouse embryo. Dev Dyn 230:174–186PubMedCrossRefGoogle Scholar
  146. Okabe N, Shimizu K, Ozaki-Kuroda K et al (2004b) Contacts between the commissural axons and the floor plate cells are mediated by nectins. Dev Biol 273:244–256PubMedCrossRefGoogle Scholar
  147. Ooshio T, Irie K, Morimoto K et al (2004) Involvement of LMO7 in the association of two cell-cell adhesion molecules, nectin and E-cadherin, through afadin and alpha-actinin in epithelial cells. J Biol Chem 279:31365–31373PubMedCrossRefGoogle Scholar
  148. Ooshio T, Fujita N, Yamada A et al (2007) Cooperative roles of Par-3 and afadin in the formation of adherens and tight junctions. J Cell Sci 120:2352–2365PubMedCrossRefGoogle Scholar
  149. Ooshio T, Kobayashi R, Ikeda W et al (2010) Involvement of the interaction of afadin with ZO-1 in the formation of tight junctions in Madin-Darby canine kidney cells. J Biol Chem 285:5003–5012PubMedPubMedCentralCrossRefGoogle Scholar
  150. Oshima T, Sato S, Kato J et al (2013) Nectin-2 is a potential target for antibody therapy of breast and ovarian cancers. Mol Cancer 12:60PubMedPubMedCentralCrossRefGoogle Scholar
  151. Ozaki-Kuroda K, Nakanishi H, Ohta H et al (2002) Nectin couples cell-cell adhesion and the actin scaffold at heterotypic testicular junctions. Curr Biol 12:1145–1150PubMedCrossRefGoogle Scholar
  152. Pavlova NN, Pallasch C, Elia AE et al (2013) A role for PVRL4-driven cell-cell interactions in tumorigenesis. Elife 2:e00358PubMedPubMedCentralCrossRefGoogle Scholar
  153. Pende D, Bottino C, Castriconi R et al (2005) PVR (CD155) and Nectin-2 (CD112) as ligands of the human DNAM-1 (CD226) activating receptor: involvement in tumor cell lysis. Mol Immunol 42:463–469PubMedCrossRefGoogle Scholar
  154. Perez-Moreno M, Fuchs E (2006) Catenins: keeping cells from getting their signals crossed. Dev Cell 11:601–612PubMedPubMedCentralCrossRefGoogle Scholar
  155. Perez-Moreno M, Jamora C, Fuchs E (2003) Sticky business: orchestrating cellular signals at adherens junctions. Cell 112:535–548PubMedCrossRefGoogle Scholar
  156. Petrova YI, Spano MM, Gumbiner BM (2012) Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion. Mol Biol Cell 23:2092–2108PubMedPubMedCentralCrossRefGoogle Scholar
  157. Pokutta S, Weis WI (2007) Structure and mechanism of cadherins and catenins in cell-cell contacts. Annu Rev Cell Dev Biol 23:237–261PubMedCrossRefGoogle Scholar
  158. Pokutta S, Drees F, Takai Y et al (2002) Biochemical and structural definition of the l-afadin- and actin-binding sites of alpha-catenin. J Biol Chem 277:18868–18874PubMedPubMedCentralCrossRefGoogle Scholar
  159. Pratakpiriya W, Seki F, Otsuki N et al (2012) Nectin4 is an epithelial cell receptor for canine distemper virus and involved in neurovirulence. J Virol 86:10207–10210PubMedPubMedCentralCrossRefGoogle Scholar
  160. Rakic P (1972) Mode of cell migration to the superficial layers of fetal monkey neocortex. J Comp Neurol 145:61–83PubMedCrossRefGoogle Scholar
  161. Restivo L, Vetere G, Bontempi B et al (2009) The formation of recent and remote memory is associated with time-dependent formation of dendritic spines in the hippocampus and anterior cingulated cortex. J Neurosci 29:8209–8214CrossRefGoogle Scholar
  162. Reymond N, Fabre S, Lecocq E et al (2001) Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction. J Biol Chem 276:43205–43215PubMedCrossRefGoogle Scholar
  163. Reymond N, Garrido-Urbani S, Borg JP et al (2005) PICK-1: a scaffold protein that interacts with Nectins and JAMs at cell junctions. FEBS Lett 579:2243–2249PubMedCrossRefGoogle Scholar
  164. Rikitake Y, Takai Y (2008) Interactions of the cell adhesion molecule nectin with transmembrane and peripheral membrane proteins for pleiotropic functions. Cell Mol Life Sci 65:253–263PubMedCrossRefGoogle Scholar
  165. Rikitake Y, Mandai K, Takai Y (2012) The role of nectins in different types of cell-cell adhesion. J Cell Sci 125:3713–3722PubMedCrossRefGoogle Scholar
  166. Sakamoto Y, Ogita H, Komura H et al (2008) Involvement of nectin in inactivation of integrin alpha(v)beta(3) after the establishment of cell-cell adhesion. J Biol Chem 283:496–505PubMedCrossRefGoogle Scholar
  167. Sakisaka T, Takai Y (2004) Biology and pathology of nectins and nectin-like molecules. Curr Opin Cell Biol 16:513–521PubMedCrossRefGoogle Scholar
  168. Sakisaka T, Taniguchi T, Nakanishi H et al (2001) Requirement of interaction of nectin-1alpha/HveC with afadin for efficient cell-cell spread of herpes simplex virus type 1. J Virol 75:4734–4743PubMedPubMedCentralCrossRefGoogle Scholar
  169. Sakisaka T, Ikeda W, Ogita H et al (2007) The roles of nectins in cell adhesions: cooperation with other cell adhesion molecules and growth factor receptors. Curr Opin Cell Biol 19:593–602PubMedCrossRefGoogle Scholar
  170. Samanta D, Ramagopal UA, Rubinstein R et al (2012) Structure of Nectin-2 reveals determinants of homophilic and heterophilic interactions that control cell-cell adhesion. Proc Natl Acad Sci U S A 109:14836–14840PubMedPubMedCentralCrossRefGoogle Scholar
  171. Sandi C, Richter-Levin G (2009) From high anxiety trait to depression: a neurocognitive hypothesis. Trends Neurosci 32:312–320PubMedCrossRefGoogle Scholar
  172. Sato T, Fujita N, Yamada A et al (2006) Regulation of the assembly and adhesion activity of E-cadherin by nectin and afadin for the formation of adherens junctions in Madin-Darby canine kidney cells. J Biol Chem 281:5288–5299PubMedCrossRefGoogle Scholar
  173. Satoh-Horikawa K, Nakanishi H, Takahashi K et al (2000) Nectin-3, a new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities. J Biol Chem 275:10291–10299PubMedCrossRefGoogle Scholar
  174. Sawyer JK, Harris NJ, Slep KC et al (2009) The Drosophila afadin homologue Canoe regulates linkage of the actin cytoskeleton to adherens junctions during apical constriction. J Cell Biol 186:57–73PubMedPubMedCentralCrossRefGoogle Scholar
  175. Sekine K, Honda T, Kawauchi T (2011) The outermost region of the developing cortical plate is crucial for both the switch of the radial migration mode and the Dab1-dependent “inside-out” lamination in the neocortex. J Neurosci 31:9426–9439PubMedCrossRefGoogle Scholar
  176. Shimizu K, Takai Y (2003) Roles of the intercellular adhesion molecule nectin in intracellular signaling. J Biochem 134:631–636PubMedCrossRefGoogle Scholar
  177. Shimono Y, Rikitake Y, Mandai K et al (2012) Immunoglobulin superfamily receptors and adherens junctions. Subcell Biochem 60:137–170PubMedCrossRefGoogle Scholar
  178. Sipe CW, Lu X (2011) Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms. Development 138:3441–3449PubMedPubMedCentralCrossRefGoogle Scholar
  179. Sipe CW, Liu L, Lee J et al (2013) Lis1 mediates planar polarity of auditory hair cells through regulation of microtubule organization. Development 140:1785–1795PubMedPubMedCentralCrossRefGoogle Scholar
  180. Soriano E, Del Rio JA (2005) The cells of cajal-retzius: still a mystery one century after. Neuron 46:389–394PubMedCrossRefGoogle Scholar
  181. Sozen MA, Suzuki K, Tolarova MM et al (2001) Mutation of PVRL1 is associated with sporadic, non-syndromic cleft lip/palate in northern Venezuela. Nat Genet 29:141–142PubMedCrossRefGoogle Scholar
  182. Spacek J, Lieberman AR (1974) Ultrastructure and three-dimensional organization of synaptic glomeruli in rat somatosensory thalamus. J Anat 117:487–516PubMedPubMedCentralGoogle Scholar
  183. Spear PG, Eisenberg RJ, Cohen GH (2000) Three classes of cell surface receptors for alphaherpesvirus entry. Virology 275:1–8PubMedCrossRefGoogle Scholar
  184. Stanietsky N, Simic H, Arapovic J et al (2009) The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci U S A 106:17858–17863PubMedPubMedCentralCrossRefGoogle Scholar
  185. Sun TT, Wang Y, Cheng H et al (2014) Disrupted interaction between CFTR and AF-6/afadin aggravates malignant phenotypes of colon cancer. Biochim Biophys Acta 1843:618–628PubMedCrossRefGoogle Scholar
  186. Suzuki K, Bustos T, Spritz RA (1998) Linkage disequilibrium mapping of the gene for Margarita Island ectodermal dysplasia (ED4) to 11q23. Am J Hum Genet 63:1102–1107PubMedPubMedCentralCrossRefGoogle Scholar
  187. Suzuki K, Hu D, Bustos T et al (2000) Mutations of PVRL1, encoding a cell-cell adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal dysplasia. Nat Genet 25:427–430PubMedCrossRefGoogle Scholar
  188. Tabata H, Nakajima K (2003) Multipolar migration: the third mode of radial neuronal migration in the developing cerebral cortex. J Neurosci 23:9996–10001PubMedGoogle Scholar
  189. Tabata H, Kanatani S, Nakajima K (2009) Differences of migratory behavior between direct progeny of apical progenitors and basal progenitors in the developing cerebral cortex. Cereb Cortex 19:2092–2105PubMedCrossRefGoogle Scholar
  190. Tachibana K, Nakanishi H, Mandai K et al (2000) Two cell adhesion molecules, nectin and cadherin, interact through their cytoplasmic domain-associated proteins. J Cell Biol 150:1161–1176PubMedPubMedCentralCrossRefGoogle Scholar
  191. Takahashi K, Nakanishi H, Miyahara M et al (1999) Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein. J Cell Biol 145:539–549PubMedPubMedCentralCrossRefGoogle Scholar
  192. Takai Y, Nakanishi H (2003) Nectin and afadin: novel organizers of intercellular junctions. J Cell Sci 116:17–27PubMedCrossRefGoogle Scholar
  193. Takai Y, Irie K, Shimizu K et al (2003a) Nectins and nectin-like molecules: roles in cell adhesion, migration, and polarization. Cancer Sci 94:655–667PubMedCrossRefGoogle Scholar
  194. Takai Y, Shimizu K, Ohtsuka T (2003b) The roles of cadherins and nectins in interneuronal synapse formation. Curr Opin Neurobiol 13:520–526PubMedCrossRefGoogle Scholar
  195. Takai Y, Ikeda W, Ogita H et al (2008a) The immunoglobulin-like cell adhesion molecule nectin and its associated protein afadin. Annu Rev Cell Dev Biol 24:309–342PubMedCrossRefGoogle Scholar
  196. Takai Y, Miyoshi J, Ikeda W et al (2008b) Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation. Nat Rev Mol Cell Biol 9:603–615PubMedCrossRefGoogle Scholar
  197. Takano A, Ishikawa N, Nishino R et al (2009) Identification of nectin-4 oncoprotein as a diagnostic and therapeutic target for lung cancer. Cancer Res 69:6694–6703PubMedCrossRefGoogle Scholar
  198. Takei N, Miyashita A, Tsukie T et al (2009) Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese. Genomics 93:441–448PubMedCrossRefGoogle Scholar
  199. Takeichi M (1991) Cadherin cell adhesion receptors as a morphogenetic regulator. Science 251:1451–1455PubMedCrossRefGoogle Scholar
  200. Takeichi M (2014) Dynamic contacts: rearranging adherens junctions to drive epithelial remodelling. Nat Rev Mol Cell Biol 15:397–410PubMedCrossRefGoogle Scholar
  201. Takekuni K, Ikeda W, Fujito T et al (2003) Direct binding of cell polarity protein PAR-3 to cell-cell adhesion molecule nectin at neuroepithelial cells of developing mouse. J Biol Chem 278:5497–5500PubMedCrossRefGoogle Scholar
  202. Taya Y, O’Kane S, Ferguson MW (1999) Pathogenesis of cleft palate in TGF-beta3 knockout mice. Development 126:3869–3879PubMedGoogle Scholar
  203. Taylor JM, Lin E, Susmarski N et al (2007) Alternative entry receptors for herpes simplex virus and their roles in disease. Cell Host Microbe 2:19–28PubMedPubMedCentralCrossRefGoogle Scholar
  204. Togashi H, Miyoshi J, Honda T et al (2006) Interneurite affinity is regulated by heterophilic nectin interactions in concert with the cadherin machinery. J Cell Biol 174:141–151PubMedPubMedCentralCrossRefGoogle Scholar
  205. Togashi H, Kominami K, Waseda M et al (2011) Nectins establish a checkerboard-like cellular pattern in the auditory epithelium. Science 333:1144–1147PubMedCrossRefGoogle Scholar
  206. Toyoshima D, Mandai K, Maruo T et al (2014) Afadin regulates puncta adherentia junction formation and presynaptic differentiation in hippocampal neurons. PLoS One 9:e89763PubMedPubMedCentralCrossRefGoogle Scholar
  207. Tsukasaki Y, Kitamura K, Shimizu K et al (2007) Role of multiple bonds between the single cell adhesion molecules, nectin and cadherin, revealed by high sensitive force measurements. J Mol Biol 367:996–1006PubMedCrossRefGoogle Scholar
  208. Tsukita S, Yamazaki Y, Katsuno T et al (2008) Tight junction-based epithelial microenvironment and cell proliferation. Oncogene 27:6930–6938PubMedCrossRefGoogle Scholar
  209. Uchida N, Honjo Y, Johnson KR et al (1996) The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones. J Cell Biol 135:767–779PubMedCrossRefGoogle Scholar
  210. Umeda K, Iwasawa N, Negishi M et al (2015) A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner. Mol Biol Cell 26:1957–1970Google Scholar
  211. van der Kooij MA, Fantin M, Rejmak E et al (2014) Role of MMP-9 in stress-induced downregulation of nectin-3 in hippocampal CA1 and associated behavioural alterations. Nat Commun 5:4995PubMedPubMedCentralCrossRefGoogle Scholar
  212. Wagner C, Batiz LF, Rodríguez S et al (2003) Cellular mechanisms involved in the stenosis and obliteration of the cerebral aqueduct of hyh mutant mice developing congenital hydrocephalus. J Neuropathol Exp Neurol 62:1019–1040PubMedCrossRefGoogle Scholar
  213. Wang XD, Chen Y, Wolf M et al (2011) Forebrain CRHR1 deficiency attenuates chronic stress-induced cognitive deficits and dendritic remodeling. Neurobiol Dis 42:300–310PubMedPubMedCentralCrossRefGoogle Scholar
  214. Wang XD, Su YA, Wagner KV et al (2013) Nectin-3 links CRHR1 signaling to stress-induced memory deficits and spine loss. Nat Neurosci 16:706–713PubMedCrossRefGoogle Scholar
  215. Wei L, Roberts W, Wang L et al (2001) Rho kinases play an obligatory role in vertebrate embryonic organogenesis. Development 128:2953–2962PubMedGoogle Scholar
  216. Wildenberg GA, Dohn MR, Carnahan RH et al (2006) p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho. Cell 127:1027–1039PubMedCrossRefGoogle Scholar
  217. Xie Z, Huganir RL, Penzes P (2005) Activity-dependent dendritic spine structural plasticity is regulated by small GTPase Rap1 and its target AF-6. Neuron 48:605–618PubMedCrossRefGoogle Scholar
  218. Yagi T, Takeichi M (2000) Cadherin superfamily genes: functions, genomic organization, and neurologic diversity. Genes Dev 14:1169–1180PubMedGoogle Scholar
  219. Yamada T, Kuramitsu K, Rikitsu E et al (2013) Nectin and junctional adhesion molecule are critical cell adhesion molecules for the apico-basal alignment of adherens and tight junctions in epithelial cells. Genes Cells 18:985–998PubMedCrossRefGoogle Scholar
  220. Yamamoto H, Maruo T, Majima T et al (2013) Genetic deletion of afadin causes hydrocephalus by destruction of adherens junctions in radial glial and ependymal cells in the midbrain. PLoS One 8:e80356PubMedPubMedCentralCrossRefGoogle Scholar
  221. Yamamoto H, Mandai K, Konno D et al (2015) Impairment of radial glial scaffold-dependent neuronal migration and formation of double cortex by genetic ablation of afadin. Brain Res 1620:139–152PubMedCrossRefGoogle Scholar
  222. Yamana S, Tokiyama A, Mizutani K et al (2015) The cell adhesion molecule Necl-4/CADM4 serves as a novel regulator for contact inhibition of cell movement and proliferation. PLoS One 10:e0124259PubMedPubMedCentralCrossRefGoogle Scholar
  223. Yonemura S, Itoh M, Nagafuchi A et al (1995) Cell-to-cell adherens junction formation and actin filament organization: similarities and differences between non-polarized fibroblasts and polarized epithelial cells. J Cell Sci 108:127–142PubMedGoogle Scholar
  224. Yoshida N, Liberman MC (1999) Stereociliary anomaly in the guinea pig: effects of hair bundle rotation on cochlear sensitivity. Hear Res 131:29–38PubMedCrossRefGoogle Scholar
  225. Yoshida T, Miyoshi J, Takai Y et al (2010) Cooperation of nectin-1 and nectin-3 is required for normal ameloblast function and crown shape development in mouse teeth. Dev Dyn 239:2558–2569PubMedCrossRefGoogle Scholar
  226. Yoshida M, Shimono Y, Togashi H et al (2012) Periderm cells covering palatal shelves have tight junctions and their desquamation reduces the polarity of palatal shelf epithelial cells in palatogenesis. Genes Cells 17:455–472PubMedCrossRefGoogle Scholar
  227. Yu Z, Chan MK, O-charoenrat P et al (2005) Enhanced nectin-1 expression and herpes oncolytic sensitivity in highly migratory and invasive carcinoma. Clin Cancer Res 11:4889–4897PubMedCrossRefGoogle Scholar
  228. Yu Z, Adusumilli PS, Eisenberg DP et al (2007) Nectin-1 expression by squamous cell carcinoma is a predictor of herpes oncolytic sensitivity. Mol Ther 15:103–113PubMedCrossRefGoogle Scholar
  229. Yuste R, Bonhoeffer T (2001) Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu Rev Neurosci 24:1071–1089PubMedCrossRefGoogle Scholar
  230. Zhang Y, Sivasankar S, Nelson WJ et al (2009) Resolving cadherin interactions and binding cooperativity at the single-molecule level. Proc Natl Acad Sci U S A 106:109–114PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Japan 2016

Authors and Affiliations

  • Takeshi Fujiwara
    • 1
    • 3
  • Akira Mizoguchi
    • 1
    • 3
  • Yoshimi Takai
    • 2
    • 3
    Email author
  1. 1.Department of Neural Regeneration and Cell CommunicationMie University Graduate School of MedicineTsuJapan
  2. 2.Division of Pathogenetic Signaling, Department of Biochemistry and Molecular BiologyKobe University Graduate School of MedicineKobeJapan
  3. 3.CREST, Japan Science and Technology AgencyKobeJapan

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