Multiple types of guanine nucleotide exchange factors (GEFS) for rab small GTpases

Cell Structure and Function

Volumn 41, Issue 2, 2016, Pages 61-79

  Ishida, Morié ^a   Oguchi, Mai E ^a   Fukuda, Mitsunori ^a  

^a TOHOKU UNIVERSITY   (Japan)

Author keywords

Autophagy; Guanine nucleotide exchange factor (GEF); Longin domain; Rab cascade; Rab small GTPase

Indexed keywords

BLOC 3 COMPLEX; DENN PROTEIN; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATE; HETERODIMER GUANINE NUCLEOTIDE EXCHANGE FACTOR COMPLEX; RAB PROTEIN; RAB3GAP1 RAB3GAP2 COMPLEX; REI 1 PROTEIN; RIC1 RGP1 COMPLEX; SEC2 PROTEIN; TRAPP COMPLEX; UNCLASSIFIED DRUG; VPS9 PROTEIN;

AMINO ACID SUBSTITUTION; AUTOPHAGY; CELLULAR DISTRIBUTION; COMPLEX FORMATION; DIMERIZATION; ENDOCYTOSIS; ENDOPLASMIC RETICULUM; ENDOSOME; ENZYME SPECIFICITY; HUMAN; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN MOTIF; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN TRANSPORT; REVIEW; ANIMAL; CHEMISTRY; METABOLISM;

ANIMALS; GUANINE NUCLEOTIDE EXCHANGE FACTORS; GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATE; HUMANS; PROTEIN TRANSPORT; RAB GTP-BINDING PROTEINS;

EID: 84978877010     PISSN: 03867196     EISSN: 13473700     Source Type: Journal    
DOI: 10.1247/csf.16008     Document Type: Review

References (193)

1. Aivazian, D., Serrano, R.L., and Pfeffer, S. 2006. TIP47 is a key effector for Rab9 localization. J. Cell Biol., 173: 917–926.
2. Aktories, K. 2011. Bacterial protein toxins that modify host regulatory GTPases. Nat. Rev. Microbiol., 9: 487–498.
3. Allaire, P.D., Marat, A.L., Dall’Armi, C., Di Paolo, G., McPherson, P.S., and Ritter, B. 2010. The Connecdenn DENN domain: a GEF for Rab35 mediating cargo-specific exit from early endosomes. Mol. Cell, 37: 370–382.
4. Baets, J., De Jonghe, P., and Timmerman, V. 2014. Recent advances in Charcot-Marie-Tooth disease. Curr. Opin. Neurol., 27: 532–540.
5. Balderhaar, H.J.K. and Ungermann, C. 2013. CORVET and HOPS tethering complexes—coordinators of endosome and lysosome fusion. J. Cell Sci., 126: 1307–1316.
6. Bar-Peled, L., Chantranupong, L., Cherniack, A.D., Chen, W.W., Ottina, K.A., Grabiner, B.C., Spear, E.D., Carter, S.L., Meyerson, M., and Sabatini, D.M. 2013. A tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science, 340: 1100–1106.
7. Barr, F. and Lambright, D.G. 2010. Rab GEFs and GAPs. Curr. Opin. Cell Biol., 22: 461–470.
8. Barrowman, J., Bhandari, D., Reinisch, K., and Ferro-Novick, S. 2010. TRAPP complexes in membrane traffic: convergence through a common Rab. Nat. Rev. Mol. Cell Biol., 11: 759–763.
9. Basel-Vanagaite, L., Sarig, O., Hershkovitz, D., Fuchs-Telem, D., Rapaport, D., Gat, A., Isman, G., Shirazi, I., Shohat, M., Enk, C.D., et al. 2009. RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome. Am. J. Hum. Genet., 85: 254–263.
10. Bassik, M.C., Kampmann, M., Lebbink, R.J., Wang, S., Hein, M.Y., Poser, I., Weibezahn, J., Horlbeck, M.A., Chen, S., Mann, M., et al. 2013. A systematic mammalian genetic interaction map reveals pathways underlying ricin susceptibility. Cell, 152: 909–922.
11. Blümer, J., Rey, J., Dehmelt, L., Mazel, T., Wu, Y.-W., Bastiaens, P., Goody, R.S., and Itzen, A. 2013. RabGEFs are a major determinant for specific Rab membrane targeting. J. Cell Biol., 200: 287–300.
12. Brondyk, W.H., McKiernan, C.J., Fortner, K.A., Stabila, P., Holz, R.W., and Macara, I.G. 1995. Interaction cloning of Rabin3, a novel protein that associates with the Ras-like GTPase Rab3A. Mol. Cell. Biol., 15: 1137–1143.
13. Brunet, S. and Sacher, M. 2014. In sickness and in health: the role of TRAPP and associated proteins in disease. Traffic, 15: 803–818.
14. Burd, C.G., Mustol, P.A., Schu, P.V., and Emr, S.D. 1996. A yeast protein related to a mammalian Ras-binding protein, Vps9p, is required for localization of vacuolar proteins. Mol. Cell. Biol., 16: 2369–2377.
15. Burgo, A., Sotirakis, E., Simmler, M.-C., Verraes, A., Chamot, C., Simpson, J.C., Lanzetti, L., Proux-Gillardeaux, V., and Galli, T. 2009. Role of Varp, a Rab21 exchange factor and TI-VAMP/VAMP7 partner, in neurite growth. EMBO Rep., 10: 1117–1124.
16. Burgo, A., Proux-Gillardeaux, V., Sotirakis, E., Bun, P., Casano, A., Verraes, A., Liem, R.K.H., Formstecher, E., Coppey-Moisan, M., and Galli, T. 2012. A molecular network for the transport of the TI-VAMP/VAMP7 vesicles from cell center to periphery. Dev. Cell, 23: 166–180.
17. Burton, J.L., Burns, M.E., Gatti, E., Augustine, G.J., and De Camilli, P. 1994. Specific interactions of Mss4 with members of the Rab GTPase subfamily. EMBO J., 13: 5547–5558.
18. Cabrera, M., Nordmann, M., Perz, A., Schmedt, D., Gerondopoulos, A., Barr, F., Piehler, J., Engelbrecht-Vandré, S., and Ungermann, C. 2014. The Mon1-Ccz1 GEF activates the Rab7 GTPase Ypt7 via a longinfold-Rab interface and association with PI3P-positive membranes. J. Cell Sci., 127: 1043–1051.
19. Cabrera, M. and Ungermann, C. 2013. Guanine nucleotide exchange factors (GEFs) have a critical but not exclusive role in organelle localization of Rab GTPases. J. Biol. Chem., 288: 28704–28712.
20. Cai, H., Shim, H., Lai, C., Xie, C., Lin, X., Yang, W.J., and Chandran, J. 2008a. ALS2/alsin knockout mice and motor neuron diseases. Neurodegener. Dis., 5: 359–366.
21. Cai, Y., Chin, H.F., Lazarova, D., Menon, S., Fu, C., Cai, H., Sclafani, A., Rodgers, D.W., De La Cruz, E.M., Ferro-Novick, S., et al. 2008b. The structural basis for activation of the Rab Ypt1p by the TRAPP membrane-tethering complexes. Cell, 133: 1202–1213.
22. Calero, M., Chen, C.Z., Zhu, W., Winand, N., Havas, K.A., Gilbert, P.M., Burd, C.G., and Collins, R.N. 2003. Dual prenylation is required for Rab protein localization and function. Mol. Biol. Cell, 14: 1852–1867.
23. Carney, D.S., Davies, B.A., and Horazdovsky, B.F. 2006. Vps9 domaincontaining proteins: activators of Rab5 GTPases from yeast to neurons. Trends Cell Biol., 16: 27–35.
24. Cherfils, J. and Zeghouf, M. 2013. Regulation of small GTPases by GEFs, GAPs, and GDIs. Physiol. Rev., 93: 269–309.
25. Chiba, S., Amagai, Y., Homma, Y., Fukuda, M., and Mizuno, K. 2013. NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by switching binding specificity from phosphatidylserine to Sec15. EMBO J., 32: 874–885.
26. Colicelli, J. 2010. Signal transduction: RABGEF1 fingers RAS for ubiquitination. Curr. Biol., 20: R630–632.
27. Das, A. and Guo, W. 2011. Rabs and the exocyst in ciliogenesis, tubulogenesis and beyond. Trends Cell Biol., 21: 383–386.
28. Daste, F., Galli, T., and Tareste, D. 2015. Structure and function of longin SNAREs. J. Cell Sci., 128: 4263–4272.
29. De Franceschi, N., Wild, K., Schlacht, A., Dacks, J.B., Sinning, I., and Filippini, F. 2014. Longin and GAF domains: structural evolution and adaptation to the subcellular trafficking machinery. Traffic, 15: 104–121.
30. Deininger, K., Eder, M., Kramer, E.R., Zieglgänsberger, W., Dodt, H., Dornmair, K., Colicelli, J., and Klein, R. 2008. The Rab5 guanylate exchange factor Rin1 regulates endocytosis of the EphA4 receptor in mature excitatory neurons. Proc. Natl. Acad. Sci. USA, 105: 12539–12544.
31. Dell’Angelica, E.C. 2004. The building BLOC(k)s of lysosomes and related organelles. Curr. Opin. Cell Biol., 16: 458–464.
32. Delprato, A., Merithew, E., and Lambright, D.G. 2004. Structure, exchange determinants, and family-wide Rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5. Cell, 118: 607–617.
33. Delprato, A. and Lambright, D.G. 2007. Structural basis for Rab GTPase activation by VPS9 domain exchange factors. Nat. Struct. Mol. Biol., 14: 406–412.
34. Denef, N., Chen, Y., Weeks, S.D., Barcelo, G., and Schüpbach, T. 2008. Crag regulates epithelial architecture and polarized deposition of basement membrane proteins in Drosophila. Dev. Cell, 14: 354–364.
35. Dhaka, A., Costa, R.M., Hu, H., Irvin, D.K., Patel, A., Kornblum, H.I., Silva, A.J., O’Dell, T.J., and Colicelli, J. 2003. The RAS effector RIN1 modulates the formation of aversive memories. J. Neurosci., 23: 748–757.
36. Diekmann, Y., Seixas, E., Gouw, M., Tavares-Cadete, F., Seabra, M.C., and Pereira-Leal, J.B. 2011. Thousands of rab GTPases for the cell biologist. PLoS Comput. Biol., 7: e1002217.
37. Dong, G., Medkova, M., Novick, P., and Reinisch, K.M. 2007. A catalytic coiled coil: structural insights into the activation of the Rab GTPase Sec4p by Sec2p. Mol. Cell, 25: 455–462.
38. Eltschinger, S. and Loewith, R. 2016. TOR complexes and the maintenance of cellular homeostasis. Trends Cell Biol., 26: 148–159.
39. Erdman, R.A., Shellenberger, K.E., Overmeyer, J.H., and Maltese, W.A. 2000. Rab24 is an atypical member of the Rab GTPase family: deficient GTPase activity, GDP dissociation inhibitor interaction, and prenylation of Rab24 expressed in cultured cells. J. Biol. Chem., 275: 3848–3856.
40. Farg, M.A., Sundaramoorthy, V., Sultana, J.M., Yang, S., Atkinson, R.A., Levina, V., Halloran, M.A., Gleeson, P.A., Blair, I.P., Soo, K.Y., et al. 2014. C9ORF72, implicated in amyotrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking. Hum. Mol. Genet., 23: 3579–3595.
41. Feng, S., Knödler, A., Ren, J., Zhang, J., Zhang, X., Hong, Y., Huang, S., Peränen, J., and Guo, W. 2012. A Rab8 guanine nucleotide exchange factor-effector interaction network regulates primary ciliogenesis. J. Biol. Chem., 287: 15602–15609.
42. Fernandes, H., Franklin, E., Jollivet, F., Bliedtner, K., and Khan, A.R. 2012. Mapping the interactions between a RUN domain from DENND5/Rab6IP1 and sorting nexin 1. PLoS One, 7: e35637.
43. Figueiredo, A.C., Wasmeier, C., Tarafder, A.K., Ramalho, J.S., Baron, R.A., and Seabra, M.C. 2008. Rab3GEP is the non-redundant guanine nucleotide exchange factor for Rab27a in melanocytes. J. Biol. Chem., 283: 23209–23216.
44. Filippini, F., Rossi, V., Galli, T., Budillon, A., D’ Urso, M., and D’Esposito, M. 2001. Longins: a new evolutionary conserved VAMP family sharing a novel SNARE domain. Trends Biochem. Sci., 26: 407–409.
45. Firestein, R., Nagy, P.L., Daly, M., Huie, P., Conti, M., and Cleary, M.L. 2002. Male infertility, impaired spermatogenesis, and azoospermia in mice deficient for the pseudophosphatase Sbf1. J. Clin. Invest., 109: 1165–1172.
46. Friedman, J.R. and Voeltz, G.K. 2011. The ER in 3D: a multifunctional dynamic membrane network. Trends Cell Biol., 21: 709–717.
47. Fukuda, M. 2008. Regulation of secretory vesicle traffic by Rab small GTPases. Cell. Mol. Life Sci., 65: 2801–2813.
48. Fukuda, M. 2011. TBC proteins: GAPs for mammalian small GTPase Rab? Biosci. Rep., 31: 159–168.
49. Fukuda, M. 2016. Multiple roles of VARP in endosomal trafficking: Rabs, retromer components and R-SNARE VAMP7 meet on VARP. Traffic, 17: 709–719.
50. Fukuda, M., Kobayashi, H., Ishibashi, K., and Ohbayashi, N. 2011. Genome-wide investigation of the Rab binding activity of RUN domains: development of a novel tool that specifically traps GTPRab35. Cell Struct. Funct., 36: 155–170.
51. Fukui, K., Sasaki, T., Imazumi, K., Matsuura, Y., Nakanishi, H., and Takai, Y. 1997. Isolation and characterization of a GTPase activating protein specific for the Rab3 subfamily of small G proteins. J. Biol. Chem., 272: 4655–4658.
52. Gerondopoulos, A., Langemeyer, L., Liang, J.R., Linford, A., and Barr, F.A. 2012. BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor. Curr. Biol., 22: 2135–2139.
53. Gerondopoulos, A., Bastos, R.N., Yoshimura, S.-I., Anderson, R., Carpanini, S., Aligianis, I., Handley, M.T., and Barr, F.A. 2014. Rab18 and a Rab18 GEF complex are required for normal ER structure. J. Cell Biol., 205: 707–720.
54. Gomes, A.Q., Ali, B.R., Ramalho, J.S., Godfrey, R.F., Barral, D.C., Hume, A.N., and Seabra, M.C. 2003. Membrane targeting of Rab GTPases is influenced by the prenylation motif. Mol. Biol. Cell, 14: 1882–1899.
55. Gournier, H., Stenmark, H., Rybin, V., Lippé, R., and Zerial, M. 1998. Two distinct effectors of the small GTPase Rab5 cooperate in endocytic membrane fusion. EMBO J., 17: 1930–1940.
56. Guo, W., Roth, D., Walch-Solimena, C., and Novick, P. 1999. The exocyst is an effector for Sec4p, targeting secretory vesicles to sites of exocytosis. EMBO J., 18: 1071–1080.
57. Guo, Z., Hou, X., Goody, R.S., and Itzen, A. 2013. Intermediates in the guanine nucleotide exchange reaction of Rab8 protein catalyzed by guanine nucleotide exchange factors Rabin8 and GRAB. J. Biol. Chem., 288: 32466–32474.
58. Haas, A.K., Yoshimura, S., Stephens, D.J., Preisinger, C., Fuchs, E., and Barr, F.A. 2007. Analysis of GTPase-activating proteins: Rab1 and Rab43 are key Rabs required to maintain a functional Golgi complex in human cells. J. Cell Sci. 120: 2997–3010.
59. Hadano, S., Otomo, A., Suzuki-Utsunomiya, K., Kunita, R., Yanagisawa, Y., Showguchi-Miyata, J., Mizumura, H., and Ikeda, J.-E. 2004. ALS2CL, the novel protein highly homologous to the carboxy-terminal half of ALS2, binds to Rab5 and modulates endosome dynamics. FEBS Lett., 575: 64–70.
60. Hadano, S., Kunita, R., Otomo, A., Suzuki-Utsunomiya, K., and Ikeda, J.‑E. 2007. Molecular and cellular function of ALS2/alsin: implication of membrane dynamics in neuronal development and degeneration. Neurochem. Int., 51: 74–84.
61. Handley, M.T. and Aligianis, I.A. 2012. RAB3GAP1, RAB3GAP2 and RAB18: disease genes in Micro and Martsolf syndromes. Biochem. Soc. Trans., 40: 1394–1397.
62. Handley, M.T., Carpanini, S.M., Mali, G.R., Sidjanin, D.J., Aligianis, I.A., Jackson, I.J., and FitzPatrick, D.R. 2015. Warburg Micro syndrome is caused by RAB18 deficiency or dysregulation. Open Biol., 5: 150047.
63. Hantan, D., Yamamoto, Y., and Sakisaka, T. 2014. VAP-B binds to Rab3GAP1 at the ER: its implication in nuclear envelope formation through the ER-Golgi intermediate compartment. Kobe J. Med. Sci., 60: E48–E56.
64. Hattula, K., Furuhjelm, J., Arffman, A., and Peränen, J. 2002. A Rab8-specific GDP/GTP exchange factor is involved in actin remodeling and polarized membrane transport. Mol. Biol. Cell, 13: 3268–3280.
65. Hesketh, G.G., Pérez-Dorado, I., Jackson, L.P., Wartosch, L., Schäfer, I.B., Gray, S.R., McCoy, A.J., Zeldin, O.B., Garman, E.F., Harbour, M.E., et al. 2014. VARP is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell surface. Dev. Cell, 29: 591–606.
66. Horgan, C.P., Hanscom, S.R., and McCaffrey, M.W. 2013. GRAB is a binding partner for the Rab11a and Rab11b GTPases. Biochem. Biophys. Res. Commun., 441: 214–219.
67. Horiuchi, H., Lippé, R., McBride, H.M., Rubino, M., Woodman, P., Stenmark, H., Rybin, V., Wilm, M., Ashman, K., Mann, M., et al. 1997. A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function. Cell, 90: 1149–1159.
68. Imai, A., Ishida, M., Fukuda, M., Nashida, T., and Shimomura, H. 2013. MADD/DENN/Rab3GEP functions as a guanine nucleotide exchange factor for Rab27 during granule exocytosis of rat parotid acinar cells. Arch. Biochem. Biophys., 536: 31–37.
69. Ioannou, M.S., Bell, E.S., Girard, M., Chaineau, M., Hamlin, J.N.R., Daubaras, M., Monast, A., Park, M., Hodgson, L., and McPherson, P.S. 2015. DENND2B activates Rab13 at the leading edge of migrating cells and promotes metastatic behavior. J. Cell Biol., 208: 629–648.
70. Ito, T., Chiba, T., Ozawa, R., Yoshida, M., Hattori, M., and Sakaki, Y. 2001. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc. Natl. Acad. Sci. USA., 98: 4569–4574.
71. Itoh, T., Satoh, M., Kanno, E., and Fukuda, M. 2006. Screening for target Rabs of TBC (Tre-2/Bub2/Cdc16) domain-containing proteins based on their Rab-binding activity. Genes Cells, 11: 1023–1037.
72. Itzen, A., Pylypenko, O., Goody, R.S., Alexandrov, K., and Rak, A. 2006. Nucleotide exchange via local protein unfolding—structure of Rab8 in complex with MSS4. EMBO J., 25: 1445–1455.
73. Iwasaki, K., Staunton, J., Saifee, O., Nonet, M., and Thomas, J.H. 1997. aex-3 encodes a novel regulator of presynaptic activity in C. elegans. Neuron, 18: 613–622.
74. Jacobson, S.G., Buraczynska, M., Milam, A.H., Chen, C., Järvaläinen, M., Fujita, R., Wu, W., Huang, Y., Cideciyan, A.V., and Swaroop, A. 1997. Disease expression in X-linked retinitis pigmentosa caused by a putative null mutation in the RPGR gene. Invest. Ophthalmol. Vis. Sci., 38: 1983–1997.
75. Janson, C., Kasahara, N., Prendergast, G.C., and Colicelli, J. 2012. RIN3 is a negative regulator of mast cell responses to SCF. PLoS One, 7: e49615.
76. Jones, S., Newman, C., Liu, F., and Segev, N. 2000. The TRAPP complex is a nucleotide exchanger for Ypt1 and Ypt31/32. Mol. Biol. Cell, 11: 4403–4411.
77. Kajiho, H., Saito, K., Tsujita, K., Kontani, K., Araki, Y., Kurosu, H., and Katada, T. 2003. RIN3: a novel Rab5 GEF interacting with amphiphysin II involved in the early endocytic pathway. J. Cell Sci., 116: 4159–4168.
78. Kajiho, H., Sakurai, K., Minoda, T., Yoshikawa, M., Nakagawa, S., Fukushima, S., Kontani, K., and Katada, T. 2011. Characterization of RIN3 as a guanine nucleotide exchange factor for the Rab5 subfamily GTPase Rab31. J. Biol. Chem., 286: 24364–24373.
79. Kajiho, H., Fukushima, S., Kontani, K., and Katada, T. 2012. RINL, guanine nucleotide exchange factor Rab5-subfamily, is involved in the EphA8-degradation pathway with odin. PLoS One, 7: e30575.
80. Kälin, S., Hirschmann, D.T., Buser, D.P., and Spiess, M. 2015. Rabaptin5 is recruited to endosomes by Rab4 and Rabex5 to regulate endosome maturation. J. Cell Sci., 128: 4126–4137.
81. Kawabe, H., Sakisaka, T., Yasumi, M., Shingai, T., Izumi, G., Nagano, F., Deguchi-Tawarada, M., Takeuchi, M., Nakanishi, H., and Takai, Y. 2003. A novel rabconnectin-3-binding protein that directly binds a GDP/GTP exchange protein for Rab3A small G protein implicated in Ca2+-dependent exocytosis of neurotransmitter. Genes Cells, 8: 537–546.
82. Kim, Y.-G., Raunser, S., Munger, C., Wagner, J., Song, Y.-L., Cygler, M., Walz, T., Oh, B.-H., and Sacher, M. 2006. The architecture of the multisubunit TRAPP I complex suggests a model for vesicle tethering. Cell, 127: 817–830.
83. Kinch, L.N. and Grishin, N.V. 2006. Longin-like folds identified in CHiPS and DUF254 proteins: vesicle trafficking complexes conserved in eukaryotic evolution. Protein Sci., 15: 2669–2674.
84. Kinchen, J.M. and Ravichandran, K.S. 2010. Identification of two evolutionarily conserved genes regulating processing of engulfed apoptotic cells. Nature, 464: 778–782.
85. Kitano, M., Nakaya, M., Nakamura, T., Nagata, S., and Matsuda, M. 2008. Imaging of Rab5 activity identifies essential regulators for phagosome maturation. Nature, 453: 241–245.
86. Kloer, D.P., Rojas, R., Ivan, V., Moriyama, K., van Vlijmen, T., Murthy, N., Ghirlando, R., van der Sluijs, P., Hurley, J.H., and Bonifacino, J.S. 2010. Assembly of the biogenesis of lysosome-related organelles complex-3 (BLOC-3) and its interaction with Rab9. J. Biol. Chem., 285: 7794–7804.
87. Knödler, A., Feng, S., Zhang, J., Zhang, X., Das, A., Peränen, J., and Guo, W. 2010. Coordination of Rab8 and Rab11 in primary ciliogenesis. Proc. Natl. Acad. Sci. USA, 107: 6346–6351.
88. Kong, C., Su, X., Chen, P.-I., and Stahl, P.D. 2007. Rin1 interacts with signal-transducing adaptor molecule (STAM) and mediates epidermal growth factor receptor trafficking and degradation. J. Biol. Chem., 282: 15294–15301.
89. Koppers, M., Blokhuis, A.M., Westeneng, H.-J., Terpstra, M.L., Zundel, C.A.C., Vieira de Sá, R., Schellevis, R.D., Waite, A.J., Blake, D.J., Veldink, J.H., et al. 2015. C9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits. Ann. Neurol., 78: 426–438.
90. Kulasekaran, G., Nossova, N., Marat, A.L., Lund, I., Cremer, C., Ioannou, M.S., and McPherson, P.S. 2015. Phosphorylation-dependent regulation of connecdenn/DENND1 guanine nucleotide exchange factors. J. Biol. Chem., 290: 17999–18008.
91. Kunita, R., Otomo, A., Mizumura, H., Suzuki-Utsunomiya, K., Hadano, S., and Ikeda, J.E. 2007. The Rab5 activator ALS2/alsin acts as a novel Rac1 effector through Rac1-activated endocytosis. J. Biol. Chem., 282: 16599–16611.
92. Lai, C., Xie, C., McCormack, S.G., Chiang, H.-C., Michalak, M.K., Lin, X., Chandran, J., Shim, H., Shimoji, M., Cookson, M.R., et al. 2006. Amyotrophic lateral sclerosis 2-deficiency leads to neuronal degeneration in amyotrophic lateral sclerosis through altered AMPA receptor trafficking. J. Neurosci., 26: 11798–11806.
93. Lai, Y., Kondapalli, C., Lehneck, R., Procter, J.B., Dill, B.D., Woodroof, H.I., Gourlay, R., Peggie, M., Macartney, T.J., Corti, O., et al. 2015. Phosphoproteomic screening identifies Rab GTPases as novel downstream targets of PINK1. EMBO J., 34: 2840–2861.
94. Lamb, C.A., Yoshimori, T., and Tooze, S.A. 2013. The autophagosome: origins unknown, biogenesis complex. Nat. Rev. Mol. Cell Biol., 14: 759–774.
95. Lamb, C.A., Nühlen, S., Judith, D., Frith, D., Snijders, A.P., Behrends, C., and Tooze, S.A. 2016. TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic. EMBO J., 35: 281–301.
96. Lattante, S., Ciura, S., Rouleau, G.A., and Kabashi, E. 2015. Defining the genetic connection linking amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD). Trends Genet., 31: 263–273.
97. Levine, T.P., Daniels, R.D., Gatta, A.T., Wong, L.H., and Hayes, M.J. 2013a. The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs. Bioinformatics, 29: 499–503.
98. Levine, T.P., Daniels, R.D., Wong, L.H., Gatta, A.T., Gerondopoulos, A., and Barr, F.A. 2013b. Discovery of new Longin and Roadblock domains that form platforms for small GTPases in Ragulator and TRAPP-II. Small GTPases, 4: 62–69.
99. Levivier, E., Goud, B., Souchet, M., Calmels, T.P.G., Mornon, J.P., and Callebaut, I. 2001. uDENN, DENN, and dDENN: indissociable domains in Rab and MAP kinases signaling pathways. Biochem. Biophys. Res. Commun., 287: 688–695.
100. Li, F., Yi, L., Zhao, L., Itzen, A., Goody, R.S., and Wu, Y.-W. 2014. The role of the hypervariable C-terminal domain in Rab GTPases membrane targeting. Proc. Natl. Acad. Sci. USA, 111: 2572–2577.
101. Liegel, R.P., Handley, M.T., Ronchetti, A., Brown, S., Langemeyer, L., Linford, A., Chang, B., Morris-Rosendahl, D.J., Carpanini, S., Posmyk, R., et al. 2013. Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans. Am. J. Hum. Genet., 93: 1001–1014.
102. Linford, A., Yoshimura, S., Nunes Bastos, R., Langemeyer, L., Gerondopoulos, A., Rigden, D.J., and Barr, F.A. 2012. Rab14 and its exchange factor FAM116 link endocytic recycling and adherens junction stability in migrating cells. Dev. Cell, 22: 952–966.
103. Lodhi, I.J., Chiang, S.-H., Chang, L., Vollenweider, D., Watson, R.T., Inoue, M., Pessin, J.E., and Saltiel, A.R. 2007. Gapex-5, a Rab31 guanine nucleotide exchange factor that regulates Glut4 trafficking in adipocytes. Cell Metab., 5: 59–72.
104. Luo, H.R., Saiardi, A., Nagata, E., Ye, K., Yu, H., Jung, T.S., Luo, X., Jain, S., Sawa, A., and Snyder, S.H. 2001. GRAB: a physiologic guanine nucleotide exchange factor for Rab3A, which interacts with inositol hexakisphosphate kinase. Neuron, 31: 439–451.
105. Machner, M.P. and Isberg, R.R. 2006. Targeting of host Rab GTPase function by the intravacuolar pathogen Legionella pneumophila. Dev. Cell, 11: 47–56.
106. Mahanty, S., Ravichandran, K., Chitirala, P., Prabha, J., Jani, R.A., and Setty, S.R. 2016. Rab9A is required for delivery of cargo from recycling endosomes to melanosomes. Pigment Cell Melanoma Res., 29: 43–59.
107. Mahoney, T.R., Liu, Q., Itoh, T., Luo, S., Hadwiger, G., Vincent, R., Wang, Z.-W., Fukuda, M., and Nonet, M.L. 2006. Regulation of synaptic transmission by RAB-3 and RAB-27 in Caenorhabditis elegans. Mol. Biol. Cell, 17: 2617–2625.
108. Marat, A.L. and McPherson, P.S. 2010. The connecdenn family, Rab35 guanine nucleotide exchange factors interfacing with the clathrin machinery. J. Biol. Chem., 285: 10627–10637.
109. Marat, A.L., Dokainish, H., and McPherson, P.S. 2011. DENN domain proteins: regulators of Rab GTPases. J. Biol. Chem., 286: 13791–13800.
110. Marubashi, S., Shimada, H., Fukuda, M., and Ohbayashi, N. 2016a. RUTBC1 functions as a GTPase-activating protein for Rab32/38 and regulates melanogenic enzyme trafficking in melanocytes. J. Biol. Chem., 291: 1427–1440.
111. Marubashi, S., Ohbayashi, N., and Fukuda, M. 2016b. A Varp-binding protein, RACK1, regulates dendrite outgrowth through stabilization of Varp protein in mouse melanocytes. J. Invest. Dermatol., in press (doi: 10.1016/j.jid.2016.03.034).
112. Masutani, T., Taguchi, K., Kumanogoh, H., Nakamura, S., and Maekawa, S. 2008. Molecular interaction of neurocalcin α with alsin (ALS2). Neurosci. Lett., 438: 26–28.
113. Matsui, T. and Fukuda, M. 2013. Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4. EMBO Rep., 14: 450–457.
114. Matsui, T., Noguchi, K., and Fukuda, M. 2014. Dennd3 functions as a guanine nucleotide exchange factor for small GTPase Rab12 in mouse embryonic fibroblasts. J. Biol. Chem., 289: 13986–13995.
115. Mattera, R. and Bonifacino, J.S. 2008. Ubiquitin binding and conjugation regulate the recruitment of Rabex-5 to early endosomes. EMBO J., 27: 2484–2494.
116. McGough, I.J., Steinberg, F., Gallon, M., Yatsu, A., Ohbayashi, N., Heesom, K.J., Fukuda, M., and Cullen, P.J. 2014. Identification of molecular heterogeneity in SNX27-retromer-mediated endosome-toplasma-membrane recycling. J. Cell Sci., 127: 4940–4953.
117. Milev, M.P., Hasaj, B., Saint-Dic, D., Snounou, S., Zhao, Q., and Sacher, M. 2015. TRAMM/TrappC12 plays a role in chromosome congression, kinetochore stability, and CENP-E recruitment. J. Cell Biol., 209: 221–234.
118. Mori, Y., Matsui, T., and Fukuda, M. 2013. Rabex-5 protein regulates dendritic localization of small GTPase Rab17 and neurite morphogenesis in hippocampal neurons. J. Biol. Chem., 288: 9835–9847.
119. Morozova, N., Liang, Y., Tokarev, A.A., Chen, S.H., Cox, R., Andrejic, J., Lipatova, Z., Sciorra, V.A., Emr, S.D., and Segev, N. 2006. TRAPPII subunits are required for the specificity switch of a Ypt-Rab GEF. Nat. Cell Biol., 8: 1263–1269.
120. Murata, T., Delprato, A., Ingmundson, A., Toomre, D.K., Lambright, D.G., and Roy, C.R. 2006. The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nat. Cell Biol., 8: 971–977.
121. Murga-Zamalloa, C.A., Atkins, S.J., Peranen, J., Swaroop, A., and Khanna, H. 2010. Interaction of retinitis pigmentosa GTPase regulator (RPGR) with RAB8A GTPase: implications for cilia dysfunction and photoreceptor degeneration. Hum. Mol. Genet., 19: 3591–3598.
122. Nachury, M.V., Loktev, A.V., Zhang, Q., Westlake, C.J., Peränen, J., Merdes, A., Slusarski, D.C., Scheller, R.H., Bazan, J.F., Sheffield, V.C., et al. 2007. A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell, 129: 1201–1213.
123. Nagano, F., Sasaki, T., Fukui, K., Asakura, T., Imazumi, K., and Takai, Y. 1998. Molecular cloning and characterization of the noncatalytic subunit of the Rab3 subfamily-specific GTPase-activating protein. J. Biol. Chem., 273: 24781–24785.
124. Nishikimi, A., Ishihara, S., Ozawa, M., Etoh, K., Fukuda, M., Kinashi, T., and Katagiri, K. 2014. Rab13 acts downstream of the kinase Mst1 to deliver the integrin LFA-1 to the cell surface for lymphocyte trafficking. Sci. Signal., 7: ra72.
125. Nookala, R.K., Langemeyer, L., Pacitto, A., Ochoa-Montaño, B., Donaldson, J.C., Blaszczyk, B.K., Chirgadze, D.Y., Barr, F.A., Bazan, J.F., and Blundell, T.L. 2012. Crystal structure of folliculin reveals a hidDENN function in genetically inherited renal cancer. Open Biol., 2: 120071.
126. Nordmann, M., Cabrera, M., Perz, A., Bröcker, C., Ostrowicz, C., Engelbrecht-Vandré, S., and Ungermann, C. 2010. The Mon1-Ccz1 complex is the GEF of the late endosomal Rab7 homolog Ypt7. Curr. Biol., 20: 1654–1659.
127. Nuoffer, C., Wu, S.K., Dascher, C., and Balch, W.E. 1997. Mss4 does not function as an exchange factor for Rab in endoplasmic reticulum to Golgi transport. Mol. Biol. Cell, 8: 1305–1316.
128. Ohbayashi, N., Yatsu, A., Tamura, K., and Fukuda, M. 2012. The Rab21-GEF activity of Varp, but not its Rab32/38 effector function, is required for dendrite formation in melanocytes. Mol. Biol. Cell, 23: 669–678.
129. Ortiz, D., Medkova, M., Walch-Solimena, C., and Novick, P. 2002. Ypt32 recruits the Sec4p guanine nucleotide exchange factor, Sec2p, to secre-tory vesicles: evidence for a Rab cascade in yeast. J. Cell Biol., 157: 1005–1015.
130. Otomo, A., Hadano, S., Okada, T., Mizumura, H., Kunita, R., Nishijima, H., Showguchi-Miyata, J., Yanagisawa, Y., Kohiki, E., Suga, E., et al. 2003. ALS2, a novel guanine nucleotide exchange factor for the small GTPase Rab5, is implicated in endosomal dynamics. Hum. Mol. Genet., 12: 1671–1687.
131. Ozeki, S., Cheng, J., Tauchi-Sato, K., Hatano, N., Taniguchi, H., and Fujimoto, T. 2005. Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane. J. Cell Sci., 118: 2601–2611.
132. Panda, S.K., Wefers, B., Ortiz, O., Floss, T., Schmid, B., Haass, C., Wurst, W., and Kühn, R. 2013. Highly efficient targeted mutagenesis in mice using TALENs. Genetics, 195: 703–713.
133. Pinar, M., Arst, H.N., Pantazopoulou, A., Tagua, V.G., de los Ríos, V., Rodríguez-Salarichs, J., Díaz, J.F., and Peñalva, M.A. 2015. TRAPPII regulates exocytic Golgi exit by mediating nucleotide exchange on the Ypt31 ortholog RabERAB11. Proc. Natl. Acad. Sci. USA, 112: 4346–4351.
134. Poteryaev, D., Datta, S., Ackema, K., Zerial, M., and Spang, A. 2010. Identification of the switch in early-to-late endosome transition. Cell, 141: 497–508.
135. Pusapati, G.V., Luchetti, G., and Pfeffer, S.R. 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: 42129–42137.
136. Rouka, E., Simister, P.C., Janning, M., Kumbrink, J., Konstantinou, T., Muniz, J.R.C., Joshi, D., O’Reilly, N., Volkmer, R., Ritter, B., et al. 2015. Differential recognition preferences of the three Src homology 3 (SH3) domains from the adaptor CD2-associated protein (CD2AP) and direct association with Ras and Rab interactor 3 (RIN3). J. Biol. Chem., 290: 25275–25292.
137. Sacher, M., Kim, Y.-G., Lavie, A., Oh, B.-H., and Segev, N. 2008. The TRAPP complex: insights into its architecture and function. Traffic, 9: 2032–2042.
138. Saito, K., Murai, J., Kajiho, H., Kontani, K., Kurosu, H., and Katada, T. 2002. A novel binding protein composed of homophilic tetramer exhibits unique properties for the small GTPase Rab5. J. Biol. Chem., 277: 3412–3418.
139. Sakaguchi, A., Sato, M., Sato, K., Gengyo-Ando, K., Yorimitsu, T., Nakai, J., Hara, T., Sato, K., and Sato, K. 2015. REI-1 is a guanine nucleotide exchange factor regulating RAB-11 localization and function in C. elegans embryos. Dev. Cell, 35: 211–221.
140. Sandri, C., Caccavari, F., Valdembri, D., Camillo, C., Veltel, S., Santambrogio, M., Lanzetti, L., Bussolino, F., Ivaska, J., and Serini, G. 2012. The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling. Cell Res., 22: 1479–1501.
141. Sato, M., Sato, K., Fonarev, P., Huang, C.-J., Liou, W., and Grant, B.D. 2005. Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit. Nat. Cell Biol., 7: 559–569.
142. Sato, M., Sato, K., Liou, W., Pant, S., Harada, A., and Grant, B.D. 2008. Regulation of endocytic recycling by C. elegans Rab35 and its regulator RME-4, a coated-pit protein. EMBO J., 27: 1183–1196.
143. Sato, Y., Fukai, S., Ishitani, R., and Nureki, O. 2007. Crystal structure of the Sec4p·Sec2p complex in the nucleotide exchanging intermediate state. Proc. Natl. Acad. Sci. USA, 104: 8305–8310.
144. Schmidt, L.S. and Linehan, W.M. 2015. Molecular genetics and clinical features of Birt-Hogg-Dubé syndrome. Nat. Rev. Urol., 12: 558–569.
145. Schoebel, S., Oesterlin, L.K., Blankenfeldt, W., Goody, R.S., and Itzen, A. 2009. RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity. Mol. Cell, 36: 1060–1072.
146. Scrivens, P.J., Noueihed, B., Shahrzad, N., Hul, S., Brunet, S., and Sacher, M. 2011. C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking. Mol. Biol. Cell, 22: 2083–2093.
147. Semerdjieva, S., Shortt, B., Maxwell, E., Singh, S., Fonarev, P., Hansen, J., Schiavo, G., Grant, B.D., and Smythe, E. 2008. Coordinated regulation of AP2 uncoating from clathrin-coated vesicles by rab5 and hRME-6. J. Cell Biol., 183: 499–511.
148. Shinde, S.R. and Maddika, S. 2016. PTEN modulates EGFR late endocytic trafficking and degradation by dephosphorylating Rab7. Nat. Commun., 7: 10689.
149. Shpilka, T. and Elazar, Z. 2015. Lipid droplets regulate autophagosome biogenesis. Autophagy, 11: 2130–2131.
150. Siniossoglou, S., Peak-Chew, S.Y., and Pelham, H.R.B. 2000. Ric1p and Rgp1p form a complex that catalyses nucleotide exchange on Ypt6p. EMBO J., 19: 4885–4894.
151. Sklan, E.H., Serrano, R.L., Einav, S., Pfeffer, S.R., Lambright, D.G., and Glenn, J.S. 2007. TBC1D20 is a Rab1 GTPase-activating protein that mediates hepatitis C virus replication. J. Biol. Chem., 282: 36354–36361.
152. Solinger, J.A. and Spang, A. 2013. Tethering complexes in the endocytic pathway: CORVET and HOPS. FEBS J., 280: 2743–2757.
153. Spang, N., Feldmann, A., Huesmann, H., Bekbulat, F., Schmitt, V., Hiebel, C., Koziollek-Drechsler, I., Clement, A.M., Moosmann, B., Jung, J., et al. 2014. RAB3GAP1 and RAB3GAP2 modulate basal and rapamycininduced autophagy. Autophagy, 10: 2297–2309.
154. Suzuki-Utsunomiya, K., Hadano, S., Otomo, A., Kunita, R., Mizumura, H., Osuga, H., and Ikeda, J.-E. 2007. ALS2CL, a novel ALS2- interactor, modulates ALS2-mediated endosome dynamics. Biochem. Biophys. Res. Commun., 354: 491–497.
155. Tall, G.G., Barbieri, M.A., Stahl, P.D., and Horazdovsky, B.F. 2001. Rasactivated endocytosis is mediated by the Rab5 guanine nucleotide exchange activity of RIN1. Dev. Cell, 1: 73–82.
156. Tam, S.-Y., Tsai, M., Snouwaert, J.N., Kalesnikoff, J., Scherrer, D., Nakae, S., Chatterjea, D., Bouley, D.M., and Galli, S.J. 2004. RabGEF1 is a negative regulator of mast cell activation and skin inflammation. Nat. Immunol., 5: 844–852.
157. Tamura, K., Ohbayashi, N., Maruta, Y., Kanno, E., Itoh, T., and Fukuda, M. 2009. Varp is a novel Rab32/38-binding protein that regulates Tyrp1 trafficking in melanocytes. Mol. Biol. Cell, 20: 2900–2908.
158. Tamura, K., Ohbayashi, N., Ishibashi, K., and Fukuda, M. 2011. Structure-function analysis of VPS9-ankyrin-repeat protein (Varp) in the trafficking of tyrosinase-related protein 1 in melanocytes. J. Biol. Chem., 286: 7507–7521.
159. Tanaka, M., Miyoshi, J., Ishizaki, H., Togawa, A., Ohnishi, K., Endo, K., Matsubara, K., Mizoguchi, A., Nagano, T., Sato, M., et al. 2001. Role of Rab3 GDP/GTP exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction. Mol. Biol. Cell, 12: 1421–1430.
160. Tersar, K., Boentert, M., Berger, P., Bonneick, S., Wessig, C., Toyka, K.V., Young, P., and Suter, U. 2007. Mtmr13/Sbf2-deficient mice: an animal model for CMT4B2. Hum. Mol. Genet., 16: 2991–3001.
161. Topp, J.D., Gray, N.W., Gerard, R.D., and Horazdovsky, B.F. 2004. Alsin is a Rab5 and Rac1 guanine nucleotide exchange factor. J. Biol. Chem., 279: 24612–24623.
162. Tsai, P.-C., Lee, S.-W., Liu, Y.-W., Chu, C.-W., Chen, K.-Y., Ho, J.-C., and Lee, F.-J.S. 2008. Afi1p functions as an Arf3p polarization-specific docking factor for development of polarity. J. Biol. Chem., 283: 16915–16927.
163. Tsun, Z.-Y., Bar-Peled, L., Chantranupong, L., Zoncu, R., Wang, T., Kim, C., Spooner, E., and Sabatini, D.M. 2013. The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Mol. Cell, 52: 495–505.
164. Vetter, M., Stehle, R., Basquin, C., and Lorentzen, E. 2015. Structure of Rab11-FIP3-Rabin8 reveals simultaneous binding of FIP3 and Rabin8 effectors to Rab11. Nat. Struct. Mol. Biol., 22: 695–702.
165. Wada, M., Nakanishi, H., Satoh, A, Hirano, H., Obaishi, H., Matsuura, Y., and Takai, Y. 1997. Isolation and characterization of a GDP/GTP exchange protein specific for the Rab3 subfamily small G proteins. J. Biol. Chem., 272: 3875–3878.
166. Walch-Solimena, C., Collins, R.N., and Novick, P.J. 1997. Sec2p mediates nucleotide exchange on Sec4p and is involved in polarized delivery of post-Golgi vesicles. J. Cell Biol., 137: 1495–1509.
167. Wang, W., Sacher, M., and Ferro-Novick, S. 2000. TRAPP stimulates guanine nucleotide exchange on Ypt1p. J. Cell Biol., 151: 289–296.
168. Wang, C.-W., Stromhaug, P.E., Kauffman, E.J., Weisman, L.S., and Klionsky, D.J. 2003. Yeast homotypic vacuole fusion requires the Ccz1-Mon1 complex during the tethering/docking stage. J. Cell Biol., 163: 973–985.
169. Wang, F., Zhang, H., Zhang, X., Wang, Y., Ren, F., Zhang, X., Zhai, Y., and Chang, Z. 2008. Varp interacts with Rab38 and functions as its potential effector. Biochem. Biophys. Res. Commun., 372: 162–167.
170. Wang, J. and Deretic, D. 2015a. The Arf and Rab11 effector FIP3 acts synergistically with ASAP1 to direct Rabin8 in ciliary receptor targeting. J. Cell Sci., 128: 1375–1385.
171. Wang, J., Ren, J., Wu, B., Feng, S., Cai, G., Tuluc, F., Peränen, J., and Guo, W. 2015b. Activation of Rab8 guanine nucleotide exchange factor Rabin8 by ERK1/2 in response to EGF signaling. Proc. Natl. Acad. Sci. USA, 112: 148–153.
172. Wasmeier, C., Romao, M., Plowright, L., Bennett, D.C., Raposo, G., and Seabra, M.C. 2006. Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes. J. Cell Biol., 175: 271–281.
173. Wei, A.-H. and Li, W. 2013. Hermansky-Pudlak syndrome: pigmentary and non-pigmentary defects and their pathogenesis. Pigment Cell Melanoma Res., 26: 176–192.
174. Westlake, C.J., Baye, L.M., Nachury, M.V, Wright, K.J., Ervin, K.E., Phu, L., Chalouni, C., Beck, J.S., Kirkpatrick, D.S., Slusarski, D.C., et al. 2011. Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (TRAPPII) complex-dependent trafficking of Rabin8 to the centrosome. Proc. Natl. Acad. Sci. USA, 108: 2759–2764.
175. Woller, B., Luiskandl, S., Popovic, M., Prieler, B.E.M., Ikonge, G., Mutzl, M., Rehmann, H., and Herbst, R. 2011. Rin-like, a novel regulator of endocytosis, acts as guanine nucleotide exchange factor for Rab5a and Rab22. Biochim. Biophys. Acta, 1813: 1198–1210.
176. Wu, X., Bradley, M.J., Cai, Y., Kümmel, D., De La Cruz, E.M., Barr, F.A., and Reinisch, K.M. 2011. Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate. Proc. Natl. Acad. Sci. USA, 108: 18672–18677.
177. Wurmser, A.E., Sato, T.K., and Emr, S.D. 2000. New component of the vacuolar class C-Vps complex couples nucleotide exchange on the Ypt7 GTPase to SNARE-dependent docking and fusion. J. Cell Biol., 151: 551–562.
178. Xiong, B., Bayat, V., Jaiswal, M., Zhang, K., Sandoval, H., Charng, W.-L., Li, T., David, G., Duraine, L., Lin, Y.-Q., et al. 2012. Crag is a GEF for Rab11 required for rhodopsin trafficking and maintenance of adult photoreceptor cells. PLoS Biol., 10: e1001438.
179. Xu, J., Fotouhi, M., and McPherson, P.S. 2015. Phosphorylation of the exchange factor DENND3 by ULK in response to starvation activates Rab12 and induces autophagy. EMBO Rep., 16: 709–718.
180. Yamasaki, A., Menon, S., Yu, S., Barrowman, J., Meerloo, T., Oorschot, V., Klumperman, J., Satoh, A., and Ferro-Novick, S. 2009. mTrs130 is a component of a mammalian TRAPPII complex, a Rab1 GEF that binds to COPI-coated vesicles. Mol. Biol. Cell, 20: 4205–4215.
181. Yang, C.-W., Hojer, C.D., Zhou, M., Wu, X., Wuster, A., Lee, W.P., Yaspan, B.L., and Chan, A.C. 2016. Regulation of T cell receptor signalling by DENND1B in TH2 cells and allergic disease. Cell, 164: 141–155.
182. Yasuda, S., Morishita, S., Fujita, A., Nanao, T., Wada, N., Waguri, S., Schiavo, G., Fukuda, M., and Nakamura, T. 2016. Mon1-Ccz1 activates Rab7 only on late endosome and dissociates from lysosome in mammalian cells. J. Cell Sci., 129: 329–340.
183. Yatsu, A., Shimada, H., Ohbayashi, N., and Fukuda, M. 2015. Rab40C is a novel Varp-binding protein that promotes proteasomal degradation of Varp in melanocytes. Biol. Open, 4: 267–275.
184. Yoshida, M., Yagi, T., Furuta, Y., Takayanagi, K., Kominami, R., Takeda, N., Tokunaga, T., Chiba, J., Ikawa, Y., and Aizawa, S. 1995. A new strategy of gene trapping in ES cells using 3’RACE. Transgenic Res., 4: 277–287.
185. Yoshimura, S., Gerondopoulos, A., Linford, A., Rigden, D.J., and Barr, F.A. 2010. Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. J. Cell Biol., 191: 367–381.
186. Yu, S. and Liang, Y. 2012. A trapper keeper for TRAPP, its structures and functions. Cell. Mol. Life Sci., 69: 3933–3944.
187. Zhang, X., He, X., Fu, X.-Y., and Chang, Z. 2006. Varp is a Rab21 guanine nucleotide exchange factor and regulates endosome dynamics. J. Cell Sci., 119: 1053–1062.
188. Zhang, L., Huang, M., and Harsay, E. 2010. A chemical genetic screen for modulators of exocytic transport identifies inhibitors of a transport mechanism linked to GTR2 function. Eukaryot. Cell, 9: 116–126.
189. Zhang, D., Iyer, L.M., He, F., and Aravind, L. 2012. Discovery of novel DENN proteins: implications for the evolution of eukaryotic intracellular membrane structures and human disease. Front. Genet., 3: 283.
190. Zhang, Z., Zhang, T., Wang, S., Gong, Z., Tang, C., Chen, J., and Ding, J. 2014. Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5. Elife, 23: 3.
191. Zhen, Y. and Stenmark, H. 2015. Cellular functions of Rab GTPases at a glance. J. Cell Sci., 128: 3171–3176.
192. Zhu, H., Liang, Z., and Li, G. 2009. Rabex-5 is a Rab22 effector and mediates a Rab22-Rab5 signaling cascade in endocytosis. Mol. Biol. Cell, 20: 4720–4729.
193. Zirin, J., Nieuwenhuis, J., Samsonova, A., Tao, R., and Perrimon, N. 2015. Regulators of autophagosome formation in Drosophila muscles. PLoS Genet., 11: e1005006.