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. 2011 Aug 31;30(17):3481–3500. doi: 10.1038/emboj.2011.286

Figure 4.

Figure 4

The Rab5/Rab7 switch during endosome maturation. Normally, Rab5-GDP and Rab7-GDP reside in the cytosol bound to its GDI. Rab5 is activated to its GTP-bound and membrane-associated form by the GEF Rabex-5 on EE membranes. The Rab5 effector Rabaptin-5 binds to Rabex-5 and promotes the activation of Rab5, thus forming a positive feedback loop in which more Rab5 molecules are activated and recruited. To initiate the Rab switch, Mon1/SAND-1 complexed with Ccz1 binds to Rab5, PtdIns(3)P, and Rabex-5, causing disassociation of Rabex-5 from the membrane. This in turn terminates the feedback loop, resulting in Rab5 inactivation and disassociation. The Mon1/SAND-1–Ccz1 complex promotes (directly or indirectly) the recruitment and activation of Rab7. Members of the HOPS complex (Vps11, Vps16, Vps18, Vps33, Vps39, and Vps41) are able to bind both Rab7 and the Mon1/SAND-1–Ccz1 complex. The HOPS complex mediates membrane tethering, needed for fusion with other LEs and lysosomes. Adapted from Cabrera and Ungermann (2010).