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Rab Family of GTPases

  • Guangpu LiEmail author
  • M. Caleb Marlin
Part of the Methods in Molecular Biology book series (MIMB, volume 1298)

Abstract

Rab proteins represent the largest branch of the Ras-like small GTPase superfamily and there are 66 Rab genes in the human genome. They alternate between GTP- and GDP-bound states, which are facilitated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and function as molecular switches in regulation of intracellular membrane trafficking in all eukaryotic cells. Each Rab targets to an organelle and specify a transport step along exocytic, endocytic, and recycling pathways as well as the crosstalk between these pathways. Through interactions with multiple effectors temporally, a Rab can control membrane budding and formation of transport vesicles, vesicle movement along cytoskeleton, and membrane fusion at the target compartment. The large number of Rab proteins reflects the complexity of the intracellular transport system, which is essential for the localization and function of membrane and secretory proteins such as hormones, growth factors, and their membrane receptors. As such, Rab proteins have emerged as important regulators for signal transduction, cell growth, and differentiation. Altered Rab expression and/or activity have been implicated in diseases ranging from neurological disorders, diabetes to cancer.

Key words

Rab GTPase GTP-binding protein Membrane trafficking Vesicular transport GAP GEF Effector 

Notes

Acknowledgement

The authors’ research program is supported by the NIH/NIGMS grant R01 GM074692 (to G.L.).

References

  1. 1.
    Diekmann Y, Seixas E, Gouw M et al (2011) Thousands of rab GTPases for the cell biologist. PLoS Comput Biol 7:e1002217PubMedCentralPubMedGoogle Scholar
  2. 2.
    Klopper TH, Kienle N, Fasshauer D et al (2012) Untangling the evolution of Rab G proteins: implications of a comprehensive genomic analysis. BMC Biol 10:71PubMedCentralPubMedGoogle Scholar
  3. 3.
    Li G, Segev N (2012) Ypt/Rab GTPases and Intracellular Membrane Trafficking: an Overview. In: Li G, Segev N (eds) Rab GTPases and Membrane Trafficking. Bentham Science Publishers, Sharjah, pp 3–17Google Scholar
  4. 4.
    Rodrigues ML, Pereira-Leal JB (2012) Novel Rab GTPases. In: Li G, Segev N (eds) Rab GTPases and Membrane Trafficking. Bentham Science Publishers, Sharjah, pp 155–168Google Scholar
  5. 5.
    Hutagalung AH, Novick PJ (2011) Role of Rab GTPases in membrane traffic and cell physiology. Physiol Rev 91:119–149PubMedCentralPubMedGoogle Scholar
  6. 6.
    Pfeffer SR (2013) Rab GTPase regulation of membrane identity. Curr Opin Cell Biol 25:414–419PubMedCentralPubMedGoogle Scholar
  7. 7.
    Chavrier P, Parton RG, Hauri HP et al (1990) Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. Cell 62:317–329PubMedGoogle Scholar
  8. 8.
    Blumer J, Rey J, Dehmelt L et al (2013) RabGEFs are a major determinant for specific Rab membrane targeting. J Cell Biol 200:287–300PubMedCentralPubMedGoogle Scholar
  9. 9.
    Sivars U, Aivazian D, Pfeffer SR (2003) Yip3 catalyses the dissociation of endosomal Rab-GDI complexes. Nature 425:856–859PubMedGoogle Scholar
  10. 10.
    Soldati T, Shapiro AD, Svejstrup AB et al (1994) Membrane targeting of the small GTPase Rab9 is accompanied by nucleotide exchange. Nature 369:76–78PubMedGoogle Scholar
  11. 11.
    Ullrich O, Horiuchi H, Bucci C et al (1994) Membrane association of Rab5 mediated by GDP-dissociation inhibitor and accompanied by GDP/GTP exchange. Nature 368:157–160PubMedGoogle Scholar
  12. 12.
    Barr F, Lambright DG (2010) Rab GEFs and GAPs. Curr Opin Cell Biol 22:461–470PubMedCentralPubMedGoogle Scholar
  13. 13.
    Soldati T, Riederer MA, Pfeffer SR (1993) Rab GDI: a solubilizing and recycling factor for rab9 protein. Mol Biol Cell 4:425–434PubMedCentralPubMedGoogle Scholar
  14. 14.
    Garrett MD, Kabcenell AK, Zahner JE et al (1993) Interaction of Sec4 with GDI proteins from bovine brain, Drosophila melanogaster and Saccharomyces cerevisiae. Conservation of GDI membrane dissociation activity. FEBS Lett 331:233–238PubMedGoogle Scholar
  15. 15.
    Ullrich O, Stenmark H, Alexandrov K et al (1993) Rab GDP dissociation inhibitor as a general regulator for the membrane association of rab proteins. J Biol Chem 268:18143–18150PubMedGoogle Scholar
  16. 16.
    Carney DS, Davies BA, Horazdovsky BF (2006) Vps9 domain-containing proteins: activators of Rab5 GTPases from yeast to neurons. Trends Cell Biol 16:27–35PubMedGoogle Scholar
  17. 17.
    Nordmann M, Cabrera M, Perz A et al (2010) The Mon1-Ccz1 complex is the GEF of the late endosomal Rab7 homolog Ypt7. Curr Biol 20:1654–1659PubMedGoogle Scholar
  18. 18.
    Poteryaev D, Datta S, Ackema K et al (2010) Identification of the switch in early-to-late endosome transition. Cell 141:497–508PubMedGoogle Scholar
  19. 19.
    Jones S, Newman C, Liu F et al (2000) The TRAPP complex is a nucleotide exchanger for Ypt1 and Ypt31/32. Mol Biol Cell 11:4403–4411PubMedCentralPubMedGoogle Scholar
  20. 20.
    Wang W, Sacher M, Ferro-Novick S (2000) TRAPP stimulates guanine nucleotide exchange on Ypt1p. J Cell Biol 151:289–296PubMedCentralPubMedGoogle Scholar
  21. 21.
    Hattula K, Furuhjelm J, Arffman A et al (2002) A Rab8-specific GDP/GTP exchange factor is involved in actin remodeling and polarized membrane transport. Mol Biol Cell 13:3268–3280PubMedCentralPubMedGoogle Scholar
  22. 22.
    Siniossoglou S, Peak-Chew SY, Pelham HR (2000) Ric1p and Rgp1p form a complex that catalyses nucleotide exchange on Ypt6p. EMBO J 19:4885–4894PubMedCentralPubMedGoogle Scholar
  23. 23.
    Marat AL, Dokainish H, McPherson PS (2011) DENN domain proteins: regulators of Rab GTPases. J Biol Chem 286:13791–13800PubMedCentralPubMedGoogle Scholar
  24. 24.
    Pan X, Eathiraj S, Munson M et al (2006) TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism. Nature 442:303–306PubMedGoogle Scholar
  25. 25.
    Ortiz D, Medkova M, Walch-Solimena C et al (2002) Ypt32 recruits the Sec4p guanine nucleotide exchange factor, Sec2p, to secretory vesicles; evidence for a Rab cascade in yeast. J Cell Biol 157:1005–1015PubMedCentralPubMedGoogle Scholar
  26. 26.
    Knodler A, Feng S, Zhang J et al (2010) Coordination of Rab8 and Rab11 in primary ciliogenesis. Proc Natl Acad Sci U S A 107:6346–6351PubMedCentralPubMedGoogle Scholar
  27. 27.
    Pusapati GV, Luchetti G, Pfeffer SR (2012) Ric1-Rgp1 complex is a guanine nucleotide exchange factor for the late Golgi Rab6A GTPase and an effector of the medial Golgi Rab33B GTPase. J Biol Chem 287:42129–42137PubMedCentralPubMedGoogle Scholar
  28. 28.
    Zhu H, Liang Z, Li G (2009) Rabex-5 is a Rab22 effector and mediates a Rab22-Rab5 signaling cascade in endocytosis. Mol Biol Cell 20:4720–4729PubMedCentralPubMedGoogle Scholar
  29. 29.
    Gerondopoulos A, Langemeyer L, Liang JR et al (2012) BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor. Curr Biol 22:2135–2139PubMedCentralPubMedGoogle Scholar
  30. 30.
    Kloer DP, Rojas R, Ivan V et al (2010) Assembly of the biogenesis of lysosome-related organelles complex-3 (BLOC-3) and its interaction with Rab9. J Biol Chem 285:7794–7804PubMedCentralPubMedGoogle Scholar
  31. 31.
    Rivera-Molina FE, Novick PJ (2009) A Rab GAP cascade defines the boundary between two Rab GTPases on the secretory pathway. Proc Natl Acad Sci U S A 106:14408–14413PubMedCentralPubMedGoogle Scholar
  32. 32.
    Nottingham RM, Pusapati GV, Ganley IG et al (2012) RUTBC2 protein, a Rab9A effector and GTPase-activating protein for Rab36. J Biol Chem 287:22740–22748PubMedCentralPubMedGoogle Scholar
  33. 33.
    Nottingham RM, Ganley IG, Barr FA et al (2011) RUTBC1 protein, a Rab9A effector that activates GTP hydrolysis by Rab32 and Rab33B proteins. J Biol Chem 286:33213–33222PubMedCentralPubMedGoogle Scholar
  34. 34.
    Nottingham RM, Pfeffer SR (2009) Defining the boundaries: Rab GEFs and GAPs. Proc Natl Acad Sci U S A 106:14185–14186PubMedCentralPubMedGoogle Scholar
  35. 35.
    Li G, Qian H (2003) Sensitivity and specificity amplification in signal transduction. Cell Biochem Biophys 39:45–59PubMedGoogle Scholar
  36. 36.
    Barr FA (2013) Review series: Rab GTPases and membrane identity: causal or inconsequential? J Cell Biol 202:191–199PubMedCentralPubMedGoogle Scholar
  37. 37.
    Mizuno-Yamasaki E, Medkova M, Coleman J et al (2010) Phosphatidylinositol 4-phosphate controls both membrane recruitment and a regulatory switch of the Rab GEF Sec2p. Dev Cell 18:828–840PubMedCentralPubMedGoogle Scholar
  38. 38.
    Stalder D, Mizuno-Yamasaki E, Ghassemian M et al (2013) Phosphorylation of the Rab exchange factor Sec2p directs a switch in regulatory binding partners. Proc Natl Acad Sci U S A 110:19995–20002PubMedCentralPubMedGoogle Scholar
  39. 39.
    Pellinen T, Arjonen A, Vuoriluoto K et al (2006) Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of beta1-integrins. J Cell Biol 173:767–780PubMedCentralPubMedGoogle Scholar
  40. 40.
    Pellinen T, Tuomi S, Arjonen A et al (2008) Integrin trafficking regulated by Rab21 is necessary for cytokinesis. Dev Cell 15:371–385PubMedGoogle Scholar
  41. 41.
    Seachrist JL, Laporte SA, Dale LB et al (2002) Rab5 association with the angiotensin II type 1A receptor promotes Rab5 GTP binding and vesicular fusion. J Biol Chem 277:679–685PubMedGoogle Scholar
  42. 42.
    Van IJzendoorn SC, Tuvim MJ, Weimbs T et al (2002) Direct interaction between Rab3b and the polymeric immunoglobulin receptor controls ligand-stimulated transcytosis in epithelial cells. Dev Cell 2:219–228PubMedGoogle Scholar
  43. 43.
    McLauchlan H, Newell J, Morrice N et al (1998) A novel role for Rab5-GDI in ligand sequestration into clathrin-coated pits. Curr Biol 8:34–45PubMedGoogle Scholar
  44. 44.
    Carroll KS, Hanna J, Simon I et al (2001) Role of Rab9 GTPase in facilitating receptor recruitment by TIP47. Science 292:1373–1376PubMedGoogle Scholar
  45. 45.
    Lindsay AJ, Jollivet F, Horgan CP et al (2013) Identification and characterization of multiple novel Rab-myosin Va interactions. Mol Biol Cell 24:3420–3434PubMedCentralPubMedGoogle Scholar
  46. 46.
    Govindan B, Bowser R, Novick P (1995) The role of Myo2, a yeast class V myosin, in vesicular transport. J Cell Biol 128:1055–1068PubMedGoogle Scholar
  47. 47.
    Fukuda M, Kuroda TS, Mikoshiba K (2002) Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport. J Biol Chem 277:12432–12436PubMedGoogle Scholar
  48. 48.
    Wu X, Wang F, Rao K et al (2002) Rab27a is an essential component of melanosome receptor for myosin Va. Mol Biol Cell 13:1735–1749PubMedCentralPubMedGoogle Scholar
  49. 49.
    Short B, Preisinger C, Schaletzky J et al (2002) The Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes. Curr Biol 12:1792–1795PubMedGoogle Scholar
  50. 50.
    Wanschers B, van de Vorstenbosch R, Wijers M et al (2008) Rab6 family proteins interact with the dynein light chain protein DYNLRB1. Cell Motil Cytoskeleton 65:183–196PubMedGoogle Scholar
  51. 51.
    Echard A, Jollivet F, Martinez O et al (1998) Interaction of a Golgi-associated kinesin-like protein with Rab6. Science 279:580–585PubMedGoogle Scholar
  52. 52.
    Ueno H, Huang X, Tanaka Y et al (2011) KIF16B/Rab14 molecular motor complex is critical for early embryonic development by transporting FGF receptor. Dev Cell 20:60–71PubMedGoogle Scholar
  53. 53.
    Horgan CP, Hanscom SR, Jolly RS et al (2010) Rab11-FIP3 binds dynein light intermediate chain 2 and its overexpression fragments the Golgi complex. Biochem Biophys Res Commun 394:387–392PubMedGoogle Scholar
  54. 54.
    Horgan CP, Hanscom SR, Jolly RS et al (2010) Rab11-FIP3 links the Rab11 GTPase and cytoplasmic dynein to mediate transport to the endosomal-recycling compartment. J Cell Sci 123:181–191PubMedGoogle Scholar
  55. 55.
    Schonteich E, Wilson GM, Burden J et al (2008) The Rip11/Rab11-FIP5 and kinesin II complex regulates endocytic protein recycling. J Cell Sci 121:3824–3833PubMedCentralPubMedGoogle Scholar
  56. 56.
    Simon GC, Prekeris R (2008) Mechanisms regulating targeting of recycling endosomes to the cleavage furrow during cytokinesis. Biochem Soc Trans 36:391–394PubMedCentralPubMedGoogle Scholar
  57. 57.
    Hoepfner S, Severin F, Cabezas A et al (2005) Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B. Cell 121:437–450PubMedGoogle Scholar
  58. 58.
    Lo SY, Brett CL, Plemel RL et al (2012) Intrinsic tethering activity of endosomal Rab proteins. Nat Struct Mol Biol 19:40–47Google Scholar
  59. 59.
    Ohya T, Miaczynska M, Coskun U et al (2009) Reconstitution of Rab- and SNARE-dependent membrane fusion by synthetic endosomes. Nature 459:1091–1097PubMedGoogle Scholar
  60. 60.
    Simonsen A, Lippe R, Christoforidis S et al (1998) EEA1 links PI(3)K function to Rab5 regulation of endosome fusion. Nature 394:494–498PubMedGoogle Scholar
  61. 61.
    Tall GG, Hama H, DeWald DB et al (1999) The phosphatidylinositol 3-phosphate binding protein Vac1p interacts with a Rab GTPase and a Sec1p homologue to facilitate vesicle-mediated vacuolar protein sorting. Mol Biol Cell 10:1873–1889PubMedCentralPubMedGoogle Scholar
  62. 62.
    Sapperstein SK, Walter DM, Grosvenor AR et al (1995) p115 is a general vesicular transport factor related to the yeast endoplasmic reticulum to Golgi transport factor Uso1p. Proc Natl Acad Sci U S A 92:522–526PubMedCentralPubMedGoogle Scholar
  63. 63.
    Barroso M, Nelson DS, Sztul E (1995) Transcytosis-associated protein (TAP)/p115 is a general fusion factor required for binding of vesicles to acceptor membranes. Proc Natl Acad Sci U S A 92:527–531PubMedCentralPubMedGoogle Scholar
  64. 64.
    TerBush DR, Maurice T, Roth D et al (1996) The Exocyst is a multiprotein complex required for exocytosis in Saccharomyces cerevisiae. EMBO J 15:6483–6494PubMedCentralPubMedGoogle Scholar
  65. 65.
    Guo W, Roth D, Walch-Solimena C et al (1999) The exocyst is an effector for Sec4p, targeting secretory vesicles to sites of exocytosis. EMBO J 18:1071–1080PubMedCentralPubMedGoogle Scholar
  66. 66.
    Balderhaar HJ, Lachmann J, Yavavli E et al (2013) The CORVET complex promotes tethering and fusion of Rab5/Vps21-positive membranes. Proc Natl Acad Sci U S A 110:3823–3828PubMedCentralPubMedGoogle Scholar
  67. 67.
    Hickey CM, Wickner W (2010) HOPS initiates vacuole docking by tethering membranes before trans-SNARE complex assembly. Mol Biol Cell 21:2297–2305PubMedCentralPubMedGoogle Scholar
  68. 68.
    Barrowman J, Bhandari D, Reinisch K et al (2010) TRAPP complexes in membrane traffic: convergence through a common Rab. Nat Rev Mol Cell Biol 11:759–763PubMedGoogle Scholar
  69. 69.
    Sacher M, Kim YG, Lavie A et al (2008) The TRAPP complex: insights into its architecture and function. Traffic 9:2032–2042PubMedCentralPubMedGoogle Scholar
  70. 70.
    Christoforidis S, McBride HM, Burgoyne RD et al (1999) The Rab5 effector EEA1 is a core component of endosome docking. Nature 397:621–625PubMedGoogle Scholar
  71. 71.
    Miaczynska M, Christoforidis S, Giner A et al (2004) APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. Cell 116:445–456PubMedGoogle Scholar
  72. 72.
    Zhu G, Chen J, Liu J et al (2007) Structure of the APPL1 BAR-PH domain and characterization of its interaction with Rab5. EMBO J 26:3484–3493PubMedCentralPubMedGoogle Scholar
  73. 73.
    Schenck A, Goto-Silva L, Collinet C et al (2008) The endosomal protein Appl1 mediates Akt substrate specificity and cell survival in vertebrate development. Cell 133:486–497PubMedGoogle Scholar
  74. 74.
    Christoforidis S, Miaczynska M, Ashman K et al (1999) Phosphatidylinositol-3-OH kinases are Rab5 effectors. Nat Cell Biol 1:249–252PubMedGoogle Scholar
  75. 75.
    Jaber N, Dou Z, Chen JS et al (2012) Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function. Proc Natl Acad Sci U S A 109:2003–2008PubMedCentralPubMedGoogle Scholar
  76. 76.
    Simonsen A, Tooze SA (2009) Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes. J Cell Biol 186:773–782PubMedCentralPubMedGoogle Scholar
  77. 77.
    Vergne I, Roberts E, Elmaoued RA et al (2009) Control of autophagy initiation by phosphoinositide 3-phosphatase Jumpy. EMBO J 28:2244–2258PubMedCentralPubMedGoogle Scholar
  78. 78.
    Stein MP, Feng Y, Cooper KL et al (2003) Human VPS34 and p150 are Rab7 interacting partners. Traffic 4:754–771PubMedGoogle Scholar
  79. 79.
    Lipatova Z, Segev N (2012) A Ypt/Rab GTPase module makes a PAS. Autophagy 8:1271–1272PubMedGoogle Scholar
  80. 80.
    Lynch-Day MA, Bhandari D, Menon S et al (2010) Trs85 directs a Ypt1 GEF, TRAPPIII, to the phagophore to promote autophagy. Proc Natl Acad Sci U S A 107:7811–7816PubMedCentralPubMedGoogle Scholar
  81. 81.
    Wang J, Menon S, Yamasaki A et al (2013) Ypt1 recruits the Atg1 kinase to the preautophagosomal structure. Proc Natl Acad Sci U S A 110:9800–9805PubMedCentralPubMedGoogle Scholar
  82. 82.
    Verhoeven K, De Jonghe P, Coen K et al (2003) Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy. Am J Hum Genet 72:722–727PubMedCentralPubMedGoogle Scholar
  83. 83.
    Houlden H, King RH, Muddle JR et al (2004) A novel RAB7 mutation associated with ulcero-mutilating neuropathy. Ann Neurol 56:586–590PubMedGoogle Scholar
  84. 84.
    Meggouh F, Bienfait HM, Weterman MA et al (2006) Charcot-Marie-Tooth disease due to a de novo mutation of the RAB7 gene. Neurology 67:1476–1478PubMedGoogle Scholar
  85. 85.
    Zuchner S, Vance JM (2006) Molecular genetics of autosomal-dominant axonal Charcot-Marie-Tooth disease. Neuromol Med 8:63–74Google Scholar
  86. 86.
    Spinosa MR, Progida C, De Luca A et al (2008) Functional characterization of Rab7 mutant proteins associated with Charcot-Marie-Tooth type 2B disease. J Neurosci 28:1640–1648PubMedGoogle Scholar
  87. 87.
    McCray BA, Skordalakes E, Taylor JP (2010) Disease mutations in Rab7 result in unregulated nucleotide exchange and inappropriate activation. Hum Mol Genet 19:1033–1047PubMedCentralPubMedGoogle Scholar
  88. 88.
    Jenkins D, Seelow D, Jehee FS et al (2007) RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. Am J Hum Genet 80:1162–1170PubMedCentralPubMedGoogle Scholar
  89. 89.
    Olkkonen VM, Peterson JR, Dupree P et al (1994) Isolation of a mouse cDNA encoding Rab23, a small novel GTPase expressed predominantly in the brain. Gene 138:207–211PubMedGoogle Scholar
  90. 90.
    Evans TM, Ferguson C, Wainwright BJ et al (2003) Rab23, a negative regulator of hedgehog signaling, localizes to the plasma membrane and the endocytic pathway. Traffic 4:869–884PubMedGoogle Scholar
  91. 91.
    Eggenschwiler JT, Espinoza E, Anderson KV (2001) Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway. Nature 412:194–198PubMedGoogle Scholar
  92. 92.
    Griscelli C, Durandy A, Guy-Grand D et al (1978) A syndrome associating partial albinism and immunodeficiency. Am J Med 65:691–702PubMedGoogle Scholar
  93. 93.
    Menasche G, Pastural E, Feldmann J et al (2000) Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nat Genet 25:173–176PubMedGoogle Scholar
  94. 94.
    Stinchcombe JC, Barral DC, Mules EH et al (2001) Rab27a is required for regulated secretion in cytotoxic T lymphocytes. J Cell Biol 152:825–834PubMedCentralPubMedGoogle Scholar
  95. 95.
    Hume AN, Collinson LM, Rapak A et al (2001) Rab27a regulates the peripheral distribution of melanosomes in melanocytes. J Cell Biol 152:795–808PubMedCentralPubMedGoogle Scholar
  96. 96.
    Wu X, Rao K, Bowers MB et al (2001) Rab27a enables myosin Va-dependent melanosome capture by recruiting the myosin to the organelle. J Cell Sci 114:1091–1100PubMedGoogle Scholar
  97. 97.
    Wilson SM, Yip R, Swing DA et al (2000) A mutation in Rab27a causes the vesicle transport defects observed in ashen mice. Proc Natl Acad Sci U S A 97:7933–7938PubMedCentralPubMedGoogle Scholar
  98. 98.
    Di Pietro SM, Dell’Angelica EC (2005) The cell biology of Hermansky-Pudlak syndrome: recent advances. Traffic 6:525–533PubMedGoogle Scholar
  99. 99.
    Loftus SK, Larson DM, Baxter LL et al (2002) Mutation of melanosome protein RAB38 in chocolate mice. Proc Natl Acad Sci U S A 99:4471–4476PubMedCentralPubMedGoogle Scholar
  100. 100.
    Oiso N, Riddle SR, Serikawa T et al (2004) The rat Ruby (R) locus is Rab38: identical mutations in Fawn-hooded and Tester-Moriyama rats derived from an ancestral Long Evans rat sub-strain. Mamm Genome 15:307–314PubMedGoogle Scholar
  101. 101.
    Wasmeier C, Romao M, Plowright L et al (2006) Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes. J Cell Biol 175:271–281PubMedCentralPubMedGoogle Scholar
  102. 102.
    Giannandrea M, Bianchi V, Mignogna ML et al (2010) Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly. Am J Hum Genet 86:185–195PubMedCentralPubMedGoogle Scholar
  103. 103.
    Caswell PT, Spence HJ, Parsons M et al (2007) Rab25 associates with alpha5beta1 integrin to promote invasive migration in 3D microenvironments. Dev Cell 13:496–510PubMedGoogle Scholar
  104. 104.
    Cheng KW, Lahad JP, Kuo WL et al (2004) The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat Med 10:1251–1256PubMedGoogle Scholar
  105. 105.
    Nam KT, Lee HJ, Smith JJ et al (2010) Loss of Rab25 promotes the development of intestinal neoplasia in mice and is associated with human colorectal adenocarcinomas. J Clin Invest 120:840–849PubMedCentralPubMedGoogle Scholar
  106. 106.
    Dozynkiewicz MA, Jamieson NB, Macpherson I et al (2012) Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression. Dev Cell 22:131–145PubMedCentralPubMedGoogle Scholar
  107. 107.
    Ginsberg SD, Alldred MJ, Counts SE et al (2010) Microarray analysis of hippocampal CA1 neurons implicates early endosomal dysfunction during Alzheimer’s disease progression. Biol Psychiatry 68:885–893PubMedCentralPubMedGoogle Scholar
  108. 108.
    Cataldo AM, Peterhoff CM, Troncoso JC et al (2000) Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer’s disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol 157:277–286PubMedCentralPubMedGoogle Scholar
  109. 109.
    Chen Y, Wang Y, Zhang J et al (2012) Rab10 and myosin-Va mediate insulin-stimulated GLUT4 storage vesicle translocation in adipocytes. J Cell Biol 198:545–560PubMedCentralPubMedGoogle Scholar
  110. 110.
    Miinea CP, Sano H, Kane S et al (2005) AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain. Biochem J 391:87–93PubMedCentralPubMedGoogle Scholar
  111. 111.
    Zeigerer A, McBrayer MK, McGraw TE (2004) Insulin stimulation of GLUT4 exocytosis, but not its inhibition of endocytosis, is dependent on RabGAP AS160. Mol Biol Cell 15:4406–4415PubMedCentralPubMedGoogle Scholar
  112. 112.
    Sano H, Kane S, Sano E et al (2003) Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation. J Biol Chem 278:14599–14602PubMedGoogle Scholar

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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA

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