RAB9 GEFs exchange GTP for GDP on RAB9

RAB9 plays a role in the retrograde traffic of cargo such as the mannose-6-phosphate receptors (M6PR) from the late endosome to the trans-Golgi network (TGN). Vesicles are recruited to the TGN through interaction of RAB9 with the atypical RHO GTPase RHOBTB3, and tethered by virtue of interaction with TGN-localized Golgins and the GARP complex (Perez-Victoria et al, 2008; Perez-Victoria et al, 2009; Diaz et al, 1999; Espinosa et al, 2009; reviewed in Pfeffer, 2011; Chia and Gleeson, 2014). Interaction of RAB9:GDP with its GEFs promotes release of GDP, allowing GTP to bind, and precludes the interaction of RAB9 with GDI and CHM proteins. DENND2 family members have been shown to be RAB9 specific GEFs, and HeLa cells depleted of RAB9 or DENND2A show reduced staining of M6PR and a loss of M6PR-positive structures in the cell periphery (Yoshimura et al, 2010).

RAB9 在货物运输如甘露糖-6-磷酸受体（M6PR）从晚期内质网到高尔基体横管（TGN）的逆行交通中扮演着重要角色。囊泡通过RAB9与不典型RHO GTP酶RHOBTB3的相互作用被招募至TGN，并因与定位于TGN的Golgin蛋白和GARP复合物（Perez-Victoria等，2008；Perez-Victoria等，2009；Diaz等，1999；Espinosa等，2009；详见Pfeffer，2011；Chia和Gleeson，2014）的相互作用而被固定。RAB9:GDP与其GEFs的相互作用促进GDP的释放，从而允许GTP的结合，并阻止RAB9与GDI和CHM蛋白的相互作用。研究表明DENND2家族成员是RAB9特异的GEFs，而缺乏RAB9或DENND2A的HeLa细胞显示出M6PR染色减少以及细胞周边M6PR阳性结构的丧失（Yoshimura等，2010）。