RAB21 GEFs exchange GTP for GDP on RAB21

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
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
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
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
Participant Of
Catalyst Activity
Catalyst Activity
Rab guanyl-nucleotide exchange factor activity of RAB21 GEFs [cytosol]
Physical Entity
Orthologous Events
Cite Us!