NaPi-IIa interacting partners and their (un)known functional roles

  • Nati HernandoEmail author
Invited Review


The sorting and stabilization of proteins at specific subcellular domains depend upon the formation of networks build up by specific protein-protein interactions. In addition, protein networks also ensure the specificity of many regulatory processes by bringing together regulatory molecules with their targets. Whereas the success on the identification of protein-protein interactions is (up to a point) technology-driven, the assignment of functional roles to specific partners remains a major challenge. This review summarizes the work that led to the identification of partners of the Na+/phosphate cotransporter NaPi-IIa as well as the effects of the interactions in the expression and/or regulation of the cotransporter.


Renal proximal tubule Phosphate Slc34a1 NaPi-IIa Interacting proteins 


  1. 1.
    Ames JB, Lim S (2012) Molecular structure and target recognition of neuronal calcium sensor proteins. Bba-Gen Subjects 1820:1205–1213. CrossRefGoogle Scholar
  2. 2.
    Antonny B, Burd C, De Camilli P, Chen E, Daumke O, Faelber K, Ford M, Frolov VA, Frost A, Hinshaw JE, Kirchhausen T, Kozlov MM, Lenz M, Low HH, McMahon H, Merrifield C, Pollard TD, Robinson PJ, Roux A, Schmid S (2016) Membrane fission by dynamin: what we know and what we need to know. EMBO J 35:2270–2284. PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Ardura JA, Wang B, Watkins SC, Vilardaga JP, Friedman PA (2011) Dynamic Na+-H+ exchanger regulatory factor-1 association and dissociation regulate parathyroid hormone receptor trafficking at membrane microdomains. J Biol Chem 286:35020–35029. PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Bacic D, Kaissling B, McLeroy P, Zou L, Baum M, Moe OW (2003) Dopamine acutely decreases apical membrane Na/H exchanger NHE3 protein in mouse renal proximal tubule. Kidney Int 64:2133–2141. PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Bergwitz C, Juppner H (2010) Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annu Rev Med 61:91–104. PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Biber J, Hernando N, Forster I (2013) Phosphate transporters and their function. Annu Rev Physiol 75:535–550. PubMedCrossRefGoogle Scholar
  7. 7.
    Bonifacino JS, Rojas R (2006) Retrograde transport from endosomes to the trans-Golgi network. Nat Rev Mol Cell Biol 7:568–579. PubMedCrossRefGoogle Scholar
  8. 8.
    Braunewell KH, Klein-Szanto AJ (2009) Visinin-like proteins (VSNLs): interaction partners and emerging functions in signal transduction of a subfamily of neuronal Ca2+-sensor proteins. Cell Tissue Res 335:301–316. PubMedCrossRefGoogle Scholar
  9. 9.
    Capuano P, Bacic D, Roos M, Gisler SM, Stange G, Biber J, Kaissling B, Weinman EJ, Shenolikar S, Wagner CA, Murer H (2007) Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient mice. Am J Physiol Cell Phys 292:C927–C934. CrossRefGoogle Scholar
  10. 10.
    Capuano P, Bacic D, Stange G, Hernando N, Kaissling B, Pal R, Kocher O, Biber J, Wagner CA, Murer H (2005) Expression and regulation of the renal Na/phosphate cotransporter NaPi-IIa in a mouse model deficient for the PDZ protein PDZK1. Pflugers Arch 449:392–402. PubMedCrossRefGoogle Scholar
  11. 11.
    Charest A, Lane K, McMahon K, Housman DE (2001) Association of a novel PDZ domain-containing peripheral Golgi protein with the Q-SNARE (Q-soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein receptor) protein syntaxin 6. J Biol Chem 276:29456–29465. PubMedCrossRefGoogle Scholar
  12. 12.
    Chen Y, Derin R, Petralia RS, Li M (2002) Actinfilin, a brain-specific actin-binding protein in postsynaptic density. J Biol Chem 277:30495–30501. PubMedCrossRefGoogle Scholar
  13. 13.
    Cheng H, Li JQ, Fazlieva R, Dai ZP, Bu ZM, Roder H (2009) Autoinhibitory interactions between the PDZ2 and C-terminal domains in the scaffolding protein NHERF1. Structure 17:660–669. PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Cheng J, Moyer BD, Milewski M, Loffing J, Ikeda M, Mickle JE, Cutting GR, Li M, Stanton BA, Guggino WB (2002) A Golgi-associated PDZ domain protein modulates cystic fibrosis transmembrane regulator plasma membrane expression. J Biol Chem 277:3520–3529. PubMedCrossRefGoogle Scholar
  15. 15.
    Colasante C, Chen J, Ahlemeyer B, Bonilla-Martinez R, Karnati S, Baumgart-Vogt E (2017) New insights into the distribution, protein abundance and subcellular localisation of the endogenous peroxisomal biogenesis proteins PEX3 and PEX19 in different organs and cell types of the adult mouse. PLoS One 12:e0183150. PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Cosen-Binker LI, Kapus A (2006) Cortactin: the gray eminence of the cytoskeleton. Physiology 21:352–361. PubMedCrossRefGoogle Scholar
  17. 17.
    Courbebaisse M, Leroy C, Bakouh N, Salaun C, Beck L, Grandchamp B, Planelles G, Hall RA, Friedlander G, Prie D (2012) A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism. PLoS One 7:e34764. PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Cuche JL, Marchand GR, Greger RF, Lang FC, Knox FG (1976) Phosphaturic effect of dopamine in dogs—possible role of intrarenally produced dopamine in phosphate regulation. J Clin Investig 58:71–76. PubMedCrossRefGoogle Scholar
  19. 19.
    Cunningham R, E X, Steplock D, Shenolikar S, Weinman EJ (2005) Defective PTH regulation of sodium-dependent phosphate transport in NHERF-1−/− renal proximal tubule cells and wild-type cells adapted to low-phosphate media. Am J Physiol Renal Physiol 289:F933–F938. PubMedCrossRefGoogle Scholar
  20. 20.
    Cunningham R, Esmaili A, Brown E, Biswas RS, Murtazina R, Donowitz M, Dijkman HB, van der Vlag J, Hogema BM, De Jonge HR, Shenolikar S, Wade JB, Weinman EJ (2008) Urine electrolyte, mineral, and protein excretion in NHERF-2 and NHERF-1 null mice. Am J Physiol Renal Physiol 294:F1001–F1007. PubMedCrossRefGoogle Scholar
  21. 21.
    Cunningham R, Steplock D, E X, Biswas RS, Wang F, Shenolikar S, Weinman EJ (2006) Adenoviral expression of NHERF-1 in NHERF-1 null mouse renal proximal tubule cells restores Npt2a regulation by low phosphate media and parathyroid hormone. Am J Physiol Renal Physiol 291:F896–F901. PubMedCrossRefGoogle Scholar
  22. 22.
    Custer M, Spindler B, Verrey F, Murer H, Biber J (1997) Identification of a new gene product (diphor-1) regulated by dietary phosphate. Am J Physiol Renal Physiol 273:F801–F806CrossRefGoogle Scholar
  23. 23.
    Daly RJ (2004) Cortactin signalling and dynamic actin networks. Biochem J 382:13–25. PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Deliot N, Hernando N, Horst-Liu Z, Gisler SM, Capuano P, Wagner CA, Bacic D, O'Brien S, Biber J, Murer H (2005) Parathyroid hormone treatment induces dissociation of type IIa Na+-P(i) cotransporter-Na+/H+ exchanger regulatory factor-1 complexes. Am J Physiol Cell Physiol 289:C159–C167. PubMedCrossRefGoogle Scholar
  25. 25.
    Dobrinskikh E, Giral H, Caldas YA, Levi M, Doctor RB (2010) Shank2 redistributes with NaPilla during regulated endocytosis. Am J Physiol Cell Physiol 299:C1324–C1334. PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Dobrinskikh E, Lanzano L, Rachelson J, Cranston D, Moldovan R, Lei T, Gratton E, Doctor RB (2013) Shank2 contributes to the apical retention and intracellular redistribution of NaPiIIa in OK cells. Am J Physiol Cell Physiol 304:C561–C573. PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Dunn HA, Ferguson SSG (2015) PDZ protein regulation of G protein-coupled receptor trafficking and signaling pathways. Mol Pharmacol 88:624–639. PubMedCrossRefGoogle Scholar
  28. 28.
    Fehon RG, McClatchey AI, Bretscher A (2010) Organizing the cell cortex: the role of ERM proteins. Nat Rev Mol Cell Biol 11:276–287. PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Feric M, Zhao B, Hoffert JD, Pisitkun T, Knepper MA (2011) Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule. Am J Physiol Cell Physiol 300:C755–C770. PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Fields S, Song O (1989) A novel genetic system to detect protein-protein interactions. Nature 340:245–246. PubMedCrossRefGoogle Scholar
  31. 31.
    Fievet BT, Gautreau A, Roy C, Del Maestro L, Mangeat P, Louvard D, Arpin M (2004) Phosphoinositide binding and phosphorylation act sequentially in the activation mechanism of ezrin. J Cell Biol 164:653–659. PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Fouassier L, Yun CC, Fitz JG, Doctor RB (2000) Evidence for ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) self-association through PDZ-PDZ interactions. J Biol Chem 275:25039–25045. PubMedCrossRefGoogle Scholar
  33. 33.
    Fritschy JM, Panzanelli P (2014) GABAA receptors and plasticity of inhibitory neurotransmission in the central nervous system. Eur J Neurosci 39:1845–1865. PubMedCrossRefGoogle Scholar
  34. 34.
    Gary R, Bretscher A (1995) Ezrin self-association involves binding of an N-terminal domain to a normally masked C-terminal domain that includes the F-actin binding site. Mol Biol Cell 6:1061–1075PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Gisler SM, Kittanakom S, Fuster D, Wong V, Bertic M, Radanovic T, Hall RA, Murer H, Biber J, Markovich D, Moe OW, Stagljar I (2008) Monitoring protein-protein interactions between the mammalian integral membrane transporters and PDZ-interacting partners using a modified split-ubiquitin membrane yeast two-hybrid system. Mol Cell Proteomics 7:1362–1377. PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Gisler SM, Madjdpour C, Bacic D, Pribanic S, Taylor SS, Biber J, Murer H (2003) PDZK1: II. An anchoring site for the PKA-binding protein D-AKAP2 in renal proximal tubular cells. Kidney Int 64:1746–1754. PubMedCrossRefGoogle Scholar
  37. 37.
    Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H (2003) PDZK1: I. A major scaffolder in brush borders of proximal tubular cells. Kidney Int 64:1733–1745. PubMedCrossRefGoogle Scholar
  38. 38.
    Gisler SM, Stagljar I, Traebert M, Bacic D, Biber J, Murer H (2001) Interaction of the type IIa Na/pi cotransporter with PDZ proteins. J Biol Chem 276:9206–9213. PubMedCrossRefGoogle Scholar
  39. 39.
    Glenney JR, Glenney P (1983) Fodrin is the general spectrin-like protein found in most cells whereas spectrin and the Tw protein have a restricted distribution. Cell 34:503–512. PubMedCrossRefGoogle Scholar
  40. 40.
    Gotte K, Girzalsky W, Linkert M, Baumgart E, Kammerer S, Kunau WH, Erdmann R (1998) Pex19p, a farnesylated protein essential for peroxisome biogenesis. Mol Cell Biol 18:616–628PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Guggino WB, Stanton BA (2006) New insights into cystic fibrosis: molecular switches that regulate CFTR. Nat Rev Mol Cell Bio 7:426–436. CrossRefGoogle Scholar
  42. 42.
    Guo YS, Sirkis DW, Schekman R (2014) Protein sorting at the trans-Golgi network. Annu Rev Cell Dev Bi 30:169–206. CrossRefGoogle Scholar
  43. 43.
    Hernando N, Deliot N, Gisler SM, Lederer E, Weinman EJ, Biber J, Murer H (2002) PDZ-domain interactions and apical expression of type IIa Na/P(i) cotransporters. Proc Natl Acad Sci U S A 99:11957–11962. PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Hernando N, Forgo J, Biber J, Murer H (2000) PTH-induced downregulation of the type IIa Na/P(i)-cotransporter is independent of known endocytic motifs. J Am Soc Nephrol: JASN 11:1961–1968PubMedGoogle Scholar
  45. 45.
    Hernando N, Wagner CA, Gisler SM, Biber J, Murer H (2004) PDZ proteins and proximal ion transport. Curr Opin Nephrol Hypertens 13:569–574. PubMedCrossRefGoogle Scholar
  46. 46.
    Hicks SW, Machamer CE (2005) Isoform-specific interaction of golgin-160 with the Golgi-associated protein PIST. J Biol Chem 280:28944–28951. PubMedCrossRefGoogle Scholar
  47. 47.
    Honegger KJ, Capuano P, Winter C, Bacic D, Stange G, Wagner CA, Biber J, Murer H, Hernando N (2006) Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC). Proc Natl Acad Sci U S A 103:803–808. PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Hu MC, Shiizaki K, Kuro-o M, Moe OW (2013) Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol 75:503–533. PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Ikemoto M, Arai H, Feng DD, Tanaka K, Aoki J, Dohmae N, Takio K, Adachi H, Tsujimoto M, Inoue K (2000) Identification of a PDZ-domain-containing protein that interacts with the scavenger receptor class B type I. Proc Natl Acad Sci U S A 97:6538–6543. PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Ito M, Iidawa S, Izuka M, Haito S, Segawa H, Kuwahata M, Ohkido I, Ohno H, Miyamoto K (2004) Interaction of a farnesylated protein with renal type IIa Na/Pi co-transporter in response to parathyroid hormone and dietary phosphate. Biochem J 377:607–616. PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Kajimoto Y, Shirai Y, Mukai H, Kuno T, Tanaka C (1993) Molecular cloning of two additional members of the neural visinin-like Ca(2+)-binding protein gene family. J Neurochem 61:1091–1096PubMedCrossRefGoogle Scholar
  52. 52.
    Karim-Jimenez Z, Hernando N, Biber J, Murer H (2000) A dibasic motif involved in parathyroid hormone-induced down-regulation of the type IIa NaPi cotransporter. Proc Natl Acad Sci U S A 97:12896–12901. PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Karim-Jimenez Z, Hernando N, Biber J, Murer H (2001) Molecular determinants for apical expression of the renal type IIa Na+/Pi-cotransporter. Pflugers Arch 442:782–790PubMedCrossRefGoogle Scholar
  54. 54.
    Karim Z, Gerard B, Bakouh N, Alili R, Leroy C, Beck L, Silve C, Planelles G, Urena-Torres P, Grandchamp B, Friedlander G, Prie D (2008) NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med 359:1128–1135. PubMedCrossRefGoogle Scholar
  55. 55.
    Keusch I, Traebert M, Lotscher M, Kaissling B, Murer H, Biber J (1998) Parathyroid hormone and dietary phosphate provoke a lysosomal routing of the proximal tubular Na/Pi-cotransporter type II. Kidney Int 54:1224–1232. PubMedCrossRefGoogle Scholar
  56. 56.
    Khundmiri SJ, Ahmad A, Bennett RE, Weinman EJ, Steplock D, Cole J, Baumann PD, Lewis J, Singh S, Clark BJ, Lederer ED (2008) Novel regulatory function for NHERF-1 in Npt2a transcription. Am J Physiol Renal Physiol 294:F840–F849. PubMedCrossRefGoogle Scholar
  57. 57.
    Khundmiri SJ, Murray RD, Lederer E (2016) PTH and vitamin D. Compr Physiol 6:561–601. PubMedCrossRefGoogle Scholar
  58. 58.
    Kocher O, Cheresh P, Brown LF, Lee SW (1995) Identification of a novel gene, selectively up-regulated in human carcinomas, using the differential display technique. Clin Cancer Res 1:1209–1215PubMedGoogle Scholar
  59. 59.
    Kocher O, Cheresh P, Lee SW (1996) Identification and partial characterization of a novel membrane-associated protein (MAP17) up-regulated in human carcinomas and modulating cell replication and tumor growth. Am J Pathol 149:493–500PubMedPubMedCentralGoogle Scholar
  60. 60.
    Kocher O, Comella N, Tognazzi K, Brown LF (1998) Identification and partial characterization of PDZK1: a novel protein containing PDZ interaction domains. Lab Invest 78:117–125PubMedGoogle Scholar
  61. 61.
    Kocher O, Pal R, Roberts M, Cirovic C, Gilchrist A (2003) Targeted disruption of the PDZK1 gene by homologous recombination. Mol Cell Biol 23:1175–1180PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Kraut N, Frampton J, Graf T (1995) Rem-1, a putative direct target gene of the Myb-Ets fusion oncoprotein in haematopoietic progenitors, is a member of the recoverin family. Oncogene 10:1027–1036PubMedGoogle Scholar
  63. 63.
    LaLonde DP, Bretscher A (2009) The scaffold protein PDZK1 undergoes a head-to-tail intramolecular association that negatively regulates its interaction with EBP50. Biochemistry-Us 48:2261–2271. CrossRefGoogle Scholar
  64. 64.
    Lanaspa MA, Caldas YA, Breusegem SY, Andres-Hernando A, Cicerchi C, Levi M, Sorribas V (2013) Inorganic phosphate modulates the expression of the NaPi-2a transporter in the trans-Golgi network and the interaction with PIST in the proximal tubule. Biomed Res Int 2013:513932–513939. PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Lanaspa MA, Giral H, Breusegem SY, Halaihel N, Baile G, Catalan J, Carrodeguas JA, Barry NP, Levi M, Sorribas V (2007) Interaction of MAP17 with NHERF3/4 induces translocation of the renal Na/pi IIa transporter to the trans-Golgi. Am J Physiol Renal Physiol 292:F230–F242. PubMedCrossRefGoogle Scholar
  66. 66.
    Leblond CS, Heinrich J, Delorme R, Proepper C, Betancur C, Huguet G, Konyukh M, Chaste P, Ey E, Rastam M, Anckarsater H, Nygren G, Gillberg IC, Melke J, Toro R, Regnault B, Fauchereau F, Mercati O, Lemiere N, Skuse D, Poot M, Holt R, Monaco AP, Jarvela I, Kantojarvi K, Vanhala R, Curran S, Collier DA, Bolton P, Chiocchetti A, Klauck SM, Poustka F, Freitag CM, Waltes R, Kopp M, Duketis E, Bacchelli E, Minopoli F, Ruta L, Battaglia A, Mazzone L, Maestrini E, Sequeira AF, Oliveira B, Vicente A, Oliveira G, Pinto D, Scherer SW, Zelenika D, Delepine M, Lathrop M, Bonneau D, Guinchat V, Devillard F, Assouline B, Mouren MC, Leboyer M, Gillberg C, Boeckers TM, Bourgeron T (2012) Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. PLoS Genet 8:e1002521. PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Li JQ, Poulikakos PI, Dai ZP, Testa JR, Callaway DJE, Bu ZM (2007) Protein kinase c phosphorylation disrupts Na+/H+ exchanger regulatory factor 1 autoinhibition and promotes cystic fibrosis transmembrane conductance regulator macromolecular assembly. J Biol Chem 282:27086–27099. PubMedCrossRefGoogle Scholar
  68. 68.
    Liem RKH (2016) Cytoskeletal integrators: the spectrin superfamily. Cold Spring Harb Perspect Biol 8:a018259. PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Lotscher M, Kaissling B, Biber J, Murer H, Levi M, Wilson P, Nguyen S (1997) Role of microtubules in the rapid regulation of renal phosphate transport in response to acute alterations in dietary phosphate content. J Clin Investig 99:1302–1312. PubMedCrossRefGoogle Scholar
  70. 70.
    Lotscher M, Scarpetta Y, Levi M, Halaihel N, Wang H, Zajicek HK, Biber J, Murer H, Kaissling B (1999) Rapid downregulation of rat renal Na/P(i) cotransporter in response to parathyroid hormone involves microtubule rearrangement. J Clin Invest 104:483–494. PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Madjdpour C, Bacic D, Kaissling B, Murer H, Biber J (2004) Segment-specific expression of sodium-phosphate cotransporters NaPi-IIa and -IIc and interacting proteins in mouse renal proximal tubules. Pflugers Arch 448:402–410. PubMedCrossRefGoogle Scholar
  72. 72.
    Mahon MJ, Donowitz M, Yun CC, Segre GV (2002) Na+/H+ exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling. Nature 417:858–861. PubMedCrossRefGoogle Scholar
  73. 73.
    Mahon MJ, Segre GV (2004) Stimulation by parathyroid hormone of a NHERF-1-assembled complex consisting of the parathyroid hormone I receptor, phospholipase C beta, and actin increases intracellular calcium in opossum kidney cells. J Biol Chem 279:23550–23558. PubMedCrossRefGoogle Scholar
  74. 74.
    Mamonova T, Zhang Q, Khajeh JA, Bu Z, Bisello A, Friedman PA (2015) Canonical and noncanonical sites determine NPT2A binding selectivity to NHERF1 PDZ1. PLoS One 10:e0129554. PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Marsell R, Krajisnik T, Goransson H, Ohlsson C, Ljunggren O, Larsson TE, Jonsson KB (2008) Gene expression analysis of kidneys from transgenic mice expressing fibroblast growth factor-23. Nephrol Dial Transplant 23:827–833. PubMedCrossRefGoogle Scholar
  76. 76.
    Matsuzono Y, Kinoshita N, Tamura S, Shimozawa N, Hamasaki M, Ghaedi K, Wanders RJ, Suzuki Y, Kondo N, Fujiki Y (1999) Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly. Proc Natl Acad Sci U S A 96:2116–2121PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    McWilliams RR, Breusegem SY, Brodsky KF, Kim E, Levi M, Doctor RB (2005) Shank2E binds NaPi cotransporter at the apical membrane of proximal tubule cells. Am J Phys Cell Phys 289:C1042–C1051. CrossRefGoogle Scholar
  78. 78.
    McWilliams RR, Gidey E, Fouassier L, Weed SA, Doctor RB (2004) Characterization of an ankyrin repeat-containing Shank2 isoform (Shank2E) in liver epithelial cells. Biochem J 380:181–191. PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Mettlen M, Chen PH, Srinivasan S, Danuser G, Schmid SL (2018) Regulation of clathrin-mediated endocytosis. Annu Rev Biochem 87:871–896. PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y (2004) In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 15:1101–1111. PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Monteiro P, Feng G (2017) SHANK proteins: roles at the synapse and in autism spectrum disorder. Nat Rev Neurosci 18:147–157. PubMedCrossRefGoogle Scholar
  82. 82.
    Morales FC, Takahashi Y, Momin S, Adams H, Chen X, Georgescu MM (2007) NHERF1/EBP50 head-to-tail intramolecular interaction masks association with PDZ domain ligands. Mol Cell Biol 27:2527–2537. PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Nakamura T, Shibata N, Nishimoto-Shibata T, Feng D, Ikemoto M, Motojima K, Iso ON, Tsukamoto K, Tsujimoto M, Arai H (2005) Regulation of SR-BI protein levels by phosphorylation of its associated protein, PDZK1. Proc Natl Acad Sci U S A 102:13404–13409. PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Neudauer CL, Joberty G, Macara IG (2001) PIST: a novel PDZ/coiled-coil domain binding partner for the rho-family GTPase TC10. Biochem Biophys Res Commun 280:541–547. PubMedCrossRefGoogle Scholar
  85. 85.
    Pearse BM, Smith CJ, Owen DJ (2000) Clathrin coat construction in endocytosis. Curr Opin Struct Biol 10:220–228PubMedCrossRefGoogle Scholar
  86. 86.
    Pfister MF, Hilfiker H, Forgo J, Lederer E, Biber J, Murer H (1998) Cellular mechanisms involved in the acute adaptation of OK cell Na/Pi-cotransport to high- or low-Pi medium. Pflugers Arch 435:713–719PubMedCrossRefGoogle Scholar
  87. 87.
    Poulat F, deSantaBarbara P, Desclozeaux M, Soullier S, Moniot B, Bonneaud N, Boizet B, Berta P (1997) The human testis determining factor SRY binds a nuclear factor containing PDZ protein interaction domains. J Biol Chem 272:7167–7172. PubMedCrossRefGoogle Scholar
  88. 88.
    Pribanic S, Gisler SM, Bacic D, Madjdpour C, Hernando N, Sorribas V, Gantenbein A, Biber J, Murer H (2003) Interactions of MAP17 with the NaPi-IIa/PDZK1 protein complex in renal proximal tubular cells. Am J Physiol Renal Physiol 285:F784–F791. PubMedCrossRefGoogle Scholar
  89. 89.
    Pribanic S, Loffing J, Madjdpour C, Bacic D, Gisler S, Braunewell KH, Biber J, Murer H (2003) Expression of visinin-like protein-3 in mouse kidney. Nephron Physiol 95:p76–p82. PubMedCrossRefGoogle Scholar
  90. 90.
    Reczek D, Berryman M, Bretscher A (1997) Identification of EBP50: a PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family. J Cell Biol 139:169–179. PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Reining SC, Gisler SM, Fuster D, Moe OW, O'Sullivan GA, Betz H, Biber J, Murer H, Hernando N (2009) GABARAP deficiency modulates expression of NaPi-IIa in renal brush-border membranes. Am J Physiol Renal Physiol 296:F1118–F1128. PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Ren AX, Zhang WQ, Yarlagadda S, Sinha C, Arora K, Moon CS, Naren AP (2013) MAST205 competes with cystic fibrosis transmembrane conductance regulator (CFTR)-associated ligand for binding to CFTR to regulate CFTR-mediated fluid transport. J Biol Chem 288:12325–12334. PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Rucktaschel R, Thoms S, Sidorovitch V, Halbach A, Pechlivanis M, Volkmer R, Alexandrov K, Kuhlmann J, Rottensteiner H, Erdmann R (2009) Farnesylation of pex19p is required for its structural integrity and function in peroxisome biogenesis. J Biol Chem 284:20885–20896. PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Sala C, Vicidomini C, Bigi I, Mossa A, Verpelli C (2015) Shank synaptic scaffold proteins: keys to understanding the pathogenesis of autism and other synaptic disorders. J Neurochem 135:849–858. PubMedCrossRefGoogle Scholar
  95. 95.
    Sarma GN, Moody IS, Ilouz R, Phan RH, Sankaran B, Hall RA, Taylor SS (2015) D-AKAP2:PKA RII:PDZK1 ternary complex structure: insights from the nucleation of a polyvalent scaffold. Protein Sci 24:105–116. PubMedCrossRefGoogle Scholar
  96. 96.
    Schaaf MBE, Keulers TG, Vooijs MA, Rouschop KMA (2016) LC3/GABARAP family proteins: autophagy-(un) related functions. FASEB J 30:3961–3978. PubMedCrossRefGoogle Scholar
  97. 97.
    Schmeisser MJ, Ey E, Wegener S, Bockmann J, Stempel AV, Kuebler A, Janssen AL, Udvardi PT, Shiban E, Spilker C, Balschun D, Skryabin BV, Dieck S, Smalla KH, Montag D, Leblond CS, Faure P, Torquet N, Le Sourd AM, Toro R, Grabrucker AM, Shoichet SA, Schmitz D, Kreutz MR, Bourgeron T, Gundelfinger ED, Boeckers TM (2012) Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature 486:256–260. PubMedCrossRefGoogle Scholar
  98. 98.
    Scott RO, Thelin WM, Milgram SL (2002) A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor. J Biol Chem 277:22934–22941. PubMedCrossRefGoogle Scholar
  99. 99.
    Shenolikar S, Minkoff CM, Steplock DA, Evangelista C, Liu MZ, Weinman EJ (2001) N-terminal PDZ domain is required for NHERF dimerization. FEBS Lett 489:233–236. PubMedCrossRefGoogle Scholar
  100. 100.
    Shenolikar S, Voltz JW, Cunningham R, Weinman EJ (2004) Regulation of ion transport by the NHERF family of PDZ proteins. Physiology 19:362–369. PubMedCrossRefGoogle Scholar
  101. 101.
    Shenolikar S, Voltz JW, Minkoff CM, Wade JB, Weinman EJ (2002) Targeted disruption of the mouse NHERF-1 gene promotes internalization of proximal tubule sodium-phosphate cotransporter type IIa and renal phosphate wasting. Proc Natl Acad Sci U S A 99:11470–11475. PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Shpilka T, Weidberg H, Pietrokovski S, Elazar Z (2011) Atg8: an autophagy-related ubiquitin-like protein family. Genome Biol 12:226. PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Silver DL, Wang N, Vogel S (2003) Identification of small PDZK1-associated protein, DD96/MAP17, as a regulator of PDZK1 and plasma high density lipoprotein levels. J Biol Chem 278:28528–28532. PubMedCrossRefGoogle Scholar
  104. 104.
    Snider J, Kittanakom S, Damjanovic D, Curak J, Wong V, Stagljar I (2010) Detecting interactions with membrane proteins using a membrane two-hybrid assay in yeast. Nat Protoc 5:1281–1293. PubMedCrossRefGoogle Scholar
  105. 105.
    Spilker C, Richter K, Smalla KH, Manahan-Vaughan D, Gundelfinger ED, Braunewell KH (2000) The neuronal EF-hand calcium-binding protein visinin-like protein-3 is expressed in cerebellar Purkinje cells and shows a calcium-dependent membrane association. Neuroscience 96:121–129. PubMedCrossRefGoogle Scholar
  106. 106.
    Sugiura T, Shimizu T, Kijima A, Minakata S, Kato Y (2011) Pdz adaptors: their regulation of epithelial transporters and involvement in human diseases. J Pharm Sci 100:3620–3635. PubMedCrossRefGoogle Scholar
  107. 107.
    Sun C, Mierke DF (2005) Characterization of interactions of Na+/H+ exchanger regulatory factor-1 with the parathyroid hormone receptor and phospholipase C. J Pept Res 65:411–417. PubMedCrossRefGoogle Scholar
  108. 108.
    Takagi-Akiba M, Asanuma K, Tanida I, Tada N, Oliva Trejo JA, Nonaka K, Asanuma E, Kominami E, Ueno T, Tomino Y (2012) Doxorubicin-induced glomerulosclerosis with proteinuria in GFP-GABARAP transgenic mice. Am J Physiol Renal Physiol 302:F380–F389. PubMedCrossRefGoogle Scholar
  109. 109.
    Tang Y, Tang J, Chen ZG, Trost C, Flockerzi V, Lin M, Ramesh V, Zhu MX (2000) Association of mammalian Trp4 and phospholipase C isozymes with a PDZ domain-containing protein, NHERF. J Biol Chem 275:37559–37564. PubMedCrossRefGoogle Scholar
  110. 110.
    Traebert M, Volkl H, Biber J, Murer H, Kaissling B (2000) Luminal and contraluminal action of 1-34 and 3-34 PTH peptides on renal type IIa Na-P(i) cotransporter. Am J Physiol Renal Physiol 278:F792–F798PubMedCrossRefGoogle Scholar
  111. 111.
    Turunen O, Wahlstrom T, Vaheri A (1994) Ezrin has a Cooh-terminal actin-binding site that is conserved in the Ezrin protein family. J Cell Biol 126:1445–1453. PubMedCrossRefGoogle Scholar
  112. 112.
    Vastiau IM, Anthonio EA, Brams M, Brees C, Young SG, Van de Velde S, Wanders RJ, Mannaerts GP, Baes M, Van Veldhoven PP, Fransen M (2006) Farnesylation of Pex19p is not essential for peroxisome biogenesis in yeast and mammalian cells. Cell Mol Life Sci: CMLS 63:1686–1699. PubMedCrossRefGoogle Scholar
  113. 113.
    Wade JB, Liu J, Coleman RA, Cunningham R, Steplock DA, Lee-Kwon W, Pallone TL, Shenolikar S, Weinman EJ (2003) Localization and interaction of NHERF isoforms in the renal proximal tubule of the mouse. Am J Physiol Cell Physiol 285:C1494–C1503. PubMedCrossRefGoogle Scholar
  114. 114.
    Wade JB, Welling PA, Donowitz M, Shenolikar S, Weinman EJ (2001) Differential renal distribution of NHERF isoforms and their colocalization with NHE3, ezrin, and ROMK. Am J Phys Cell Phys 280:C192–C198CrossRefGoogle Scholar
  115. 115.
    Walden PD, Cowan NJ (1993) A novel 205-kilodalton testis-specific serine threonine protein-kinase associated with microtubules of the spermatid manchette. Mol Cell Biol 13:7625–7635. PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Wanders RJ, Waterham HR (2005) Peroxisomal disorders I: biochemistry and genetics of peroxisome biogenesis disorders. Clin Genet 67:107–133. PubMedCrossRefGoogle Scholar
  117. 117.
    Wang DS, Lee HJ, Cooper DS, Cebotaro L, Walden PD, I C, Yun CC (2006) Coexpression of MAST205 inhibits the activity of Na(+)/H(+) exchanger NHE3. Am J of Physiol Renal Physiol 290:F428–F437. CrossRefGoogle Scholar
  118. 118.
    Wang HB, Bedford FK, Brandon NJ, Moss SJ, Olsen RW (1999) GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton. Nature 397:69–72. PubMedCrossRefGoogle Scholar
  119. 119.
    Wang SS, Yue HW, Derin RB, Guggino WB, Lit M (2000) Accessory protein facilitated CFTR-CFTR interaction, a molecular mechanism to potentiate the chloride channel activity. Cell 103:169–179. PubMedCrossRefGoogle Scholar
  120. 120.
    Weinman EJ, Biswas R, Steplock D, Douglass TS, Cunningham R, Shenolikar S (2010) Sodium-hydrogen exchanger regulatory factor 1 (NHERF-1) transduces signals that mediate dopamine inhibition of sodium-phosphate co-transport in mouse kidney. J Biol Chem 285:13454–13460. PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Weinman EJ, Biswas RS, Peng G, Shen L, Turner CL, E X, Steplock D, Shenolikar S, Cunningham R (2007) Parathyroid hormone inhibits renal phosphate transport by phosphorylation of serine 77 of sodium-hydrogen exchanger regulatory factor-1. J Clin Invest 117:3412–3420. PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Weinman EJ, Boddeti A, Cunningham R, Akom M, Wang F, Wang Y, Liu J, Steplock D, Shenolikar S, Wade JB (2003) NHERF-1 is required for renal adaptation to a low-phosphate diet. Am J Physiol Renal Physiol 285:F1225–F1232. PubMedCrossRefGoogle Scholar
  123. 123.
    Weinman EJ, Hall RA, Friedman PA, Liu-Chen LY, Shenolikar S (2006) The association of NHERF adaptor proteins with G protein-coupled receptors and receptor tyrosine kinases. Annu Rev Physiol 68:491–505. PubMedCrossRefGoogle Scholar
  124. 124.
    Weinman EJ, Lederer ED (2012) NHERF-1 and the regulation of renal phosphate reabsoption: a tale of three hormones. Am J Physiol Renal Physiol 303:F321–F327. PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Weinman EJ, Steplock D, Cha BY, Kovbasnjuk O, Frost NA, Cunningham R, Shenolikar S, Blanpied TA, Donowitz M (2009) PTH transiently increases the percent mobile fraction of Npt2a in OK cells as determined by FRAP. Am J Physiol Renal Physiol 297:F1560–F1565. PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Weinman EJ, Steplock D, Shenolikar S, Biswas R (2011) Fibroblast growth factor-23-mediated inhibition of renal phosphate transport in mice requires sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) and synergizes with parathyroid hormone. J Biol Chem 286:37216–37221. PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Weinman EJ, Steplock D, Wang YP, Shenolikar S (1995) Characterization of a protein cofactor that mediates protein-kinase-a regulation of the renal brush-border membrane Na+-H+ exchanger. J Clin Investig 95:2143–2149. PubMedCrossRefGoogle Scholar
  128. 128.
    Weinman EJ, Steplock D, Zhang YH, Biswas R, Bloch RJ, Shenolikar S (2010) Cooperativity between the phosphorylation of Thr(95) and Ser(77) of NHERF-1 in the hormonal regulation of renal phosphate transport. J Biol Chem 285:25134–25138. PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Yao RJ, Maeda T, Takada S, Noda T (2001) Identification of a PDZ domain containing Golgi protein, GOPC, as an interaction partner of frizzled. Biochem Biophys Res Commun 286:771–778. PubMedCrossRefGoogle Scholar
  130. 130.
    Ye F, Zhang M (2013) Structures and target recognition modes of PDZ domains: recurring themes and emerging pictures. Biochem J 455:1–14. PubMedCrossRefGoogle Scholar
  131. 131.
    Yonemura S, Hirao M, Doi Y, Takahashi N, Kondo T, Tsukita S, Tsukita S (1998) Ezrin/radixin/moesin (ERM) proteins bind to a positively charged amino acid cluster in the juxta-membrane cytoplasmic domain of CD44, CD43, and ICAM-2. J Cell Biol 140:885–895. PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Yun CHC, Lamprecht G, Forster DV, Sider A (1998) NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin. J Biol Chem 273:25856–25863. PubMedCrossRefGoogle Scholar
  133. 133.
    Yun CHC, Oh S, Zizak M, Steplock D, Tsao S, Tse CM, Weinman EJ, Donowitz M (1997) cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein. Proc Natl Acad Sci U S A 94:3010–3015. PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of PhysiologyUniversity ZurichZurichSwitzerland

Personalised recommendations