Reactome | RAB21 GEFs exchange GTP for GDP on RAB21

RAB21 GEFs exchange GTP for GDP on RAB21

Stable Identifier

R-HSA-8876837

Type

Reaction [transition]

Species

Homo sapiens

Compartment

early endosome membrane, cytosol

ReviewStatus

5/5

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RAB21 GEFs exchange GTP for GDP on RAB21

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RAB21 is involved in the endocytosis of transferrin and EGF receptors as well as of integrins, and RAB21-mediated integrin trafficking is required for cytokinesis (Simpson et al, 2004; Pellinen et al, 2006; Pellinen et al, 2008; reviewed in Miserey-Lenkei and Colombo, 2016). In addition, RAB21 contributes to neurite and dendrite outgrowth, macrophage outgrowth and fusion of autophagosomes with lysosomes (Obayashi et al, 2012; Burgo et al, 2009; Burgo et al, 2012; Jean et al, 2012; Jean et al, 2015). RAB21 nucleotide exchange is stimulated by ANKRD27, also known as VARP (VPS9 ankyrin repeat protein), which in addition to promoting RAB21 guanyl-nucleotide exchange, also interacts with numerous RAB effectors and contributes to multiple steps of endosomal trafficking (Zhang et al, 2006; Obayashi et al, 2012; reviwed in Fukuda, 2016; Ishida et al, 2016). Other GEFs for RAB21 include the myotubularin proteins SBF1 and SBF2 (also known as MTMR5 and MTMR13) which contribute to macrophage outgrowth and fusion of autophagosomes with lysosomes (Jean et al, 2012; Jean et al, 2015). Interaction of RAB21:GDP with its GEFs promotes release of GDP, allowing GTP to bind, and precludes the interaction of RAB21 with GDI and CHM proteins.

Literature References

PubMed ID	Title	Journal	Year
22171327	The Rab21-GEF activity of Varp, but not its Rab32/38 effector function, is required for dendrite formation in melanocytes Ohbayashi, N, Yatsu, A, Tamura, K, Fukuda, M	Mol. Biol. Cell	2012
15561770	A role for the small GTPase Rab21 in the early endocytic pathway Simpson, JC, Griffiths, G, Wessling-Resnick, M, Fransen, JA, Bennett, H, Jones, AT	J. Cell. Sci.	2004
27103185	Multiple Roles of VARP in Endosomal Trafficking: Rabs, Retromer Components and R-SNARE VAMP7 Meet on VARP Fukuda, M	Traffic	2016
22705394	A molecular network for the transport of the TI-VAMP/VAMP7 vesicles from cell center to periphery Burgo, A, Proux-Gillardeaux, V, Sotirakis, E, Bun, P, Casano, A, Verraes, A, Liem, RK, Formstecher, E, Coppey-Moisan, M, Galli, T	Dev. Cell	2012
26925400	Small RAB GTPases Regulate Multiple Steps of Mitosis Miserey-Lenkei, S, Colombo, MI	Front Cell Dev Biol	2016
16754960	Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of beta1-integrins Pellinen, T, Arjonen, A, Vuoriluoto, K, Kallio, K, Fransen, JA, Ivaska, J	J. Cell Biol.	2006
22648168	Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling Jean, S, Cox, S, Schmidt, EJ, Robinson, FL, Kiger, A	Mol. Biol. Cell	2012
18804435	Integrin trafficking regulated by Rab21 is necessary for cytokinesis Pellinen, T, Tuomi, S, Arjonen, A, Wolf, M, Edgren, H, Meyer, H, Grosse, R, Kitzing, T, Rantala, JK, Kallioniemi, O, Fässler, R, Kallio, M, Ivaska, J	Dev. Cell	2008
27246931	Multiple Types of Guanine Nucleotide Exchange Factors (GEFs) for Rab Small GTPases Ishida, M, Oguchi, ME, Fukuda, M	Cell Struct. Funct.	2016
16525121	Varp is a Rab21 guanine nucleotide exchange factor and regulates endosome dynamics Zhang, X, He, X, Fu, XY, Chang, Z	J. Cell. Sci.	2006
19745841	Role of Varp, a Rab21 exchange factor and TI-VAMP/VAMP7 partner, in neurite growth Burgo, A, Sotirakis, E, Simmler, MC, Verraes, A, Chamot, C, Simpson, JC, Lanzetti, L, Proux-Gillardeaux, V, Galli, T	EMBO Rep.	2009
25648148	Starvation-induced MTMR13 and RAB21 activity regulates VAMP8 to promote autophagosome-lysosome fusion Jean, S, Cox, S, Nassari, S, Kiger, AA	EMBO Rep.	2015