early endosome membrane,
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.