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. Author manuscript; available in PMC: 2014 Aug 1.
Published in final edited form as: Curr Opin Cell Biol. 2013 Apr 29;25(4):414–419. doi: 10.1016/j.ceb.2013.04.002

Figure 2.

Figure 2

Heterodimeric Rab GEFs recruit subsequent acting Rabs as part of Rab cascades. A. On early endosomes, Rab5 recruits the kinase that generates phosphatidylinositol 3-phosphate (PI3P); Ccz1/Mon1 is then recruited to membranes containing Rab5-GTP [30] and PI3P [31]. Ccz1/Mon1 catalyzes the release of GDP from Rab7A [29; 25], thereby permitting the entry of GTP. Presumably a Rab5 GAP will be identified that is a Rab7A effector to help clear Rab5 from a newly formed, Rab7A membrane microdomain. Ccz1/Mon1 also displaces the Rab5 GEF, Rabex-5, from membranes [31]. B. On the Golgi, medial Golgi Rab33B recruits the Ric1/Rgp1 GEF for Rab6A [28]. On late endosomes, the Hps1/Hps4 GEF for Rab32 [25] is recruited to late endosomes by Rab9A [32]. D. Rab9A can also recruit RUTBC1, a GTPase activating protein that inactivates Rab32 [33]. Rab32 GDP would be a target for membrane extraction by cytoplasmic GDI protein. This would counteract the reaction in C and may be restricted to specific tissues and/or cell types.