Meta-Biol

• Pathways

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).