Rab GTPases in Osteoclastic Endomembrane Systems

Figure 2

Rab GTPase regulating cycle: example of Rab7. Rab7 is required for the transfer of the cargo from late endosomes and autophagosomes to lysosomes. Like other Rabs, Rab7 carboxy-terminus contains motif such as XXCXC, in which the two cysteines are substrate for prenylation, a lipid transfer crucial for membrane anchoring. During the maturation of endosomes, Rab5 is exchanged with Rab7, a process facilitated by the protein complex Mon1-Ccz1, a Rab7 GEF. Membrane-anchored GDP-Rab7 is then activated to GTP-Rab7 by this GEF. The activation allows the release of Mon1-Ccz1 and the recruitment FYCO1, a Rab7 effector protein, which mediates Rab7 actions, such as autophagosome transport trough microtubule at the plus-end. TBC1D15 RabGAP facilitates the inactivation of Rab7. GDP-Rab7 is recognized by a GDI and released into the cytosol to its soluble form. The soluble GDP-Rab7 will eventually be recognized by GDF, driving the GTPase to a novel vesicle to start a new cycle (adapted from [22, 23]). Abbreviations: GAP: GTPase-activating protein; GDI: GDP dissociation inhibitor; GEF: guanine–nucleotide exchange factor; REP: Rab escort protein; RGGT: Rab Geranyl-Geranyl transferase; FYCO1: FYVE-coiled coil containing protein.