Rab GTPases in Osteoclastic Endomembrane Systems

Figure 3

Autophagy basics. Autophagy proceeds by a series of ordered events controlled by a group of autophagy-related (Atg) proteins coordinating 3 major steps: (1) the initial induction and nucleation of autophagic vesicles require the activity of specific complexes, including the PI3K complex, composed of type-III PI3K and Beclin1, and the ULK1 complex. Other upstream signaling pathways regulate ULK1 complex activity, including PI3K/Akt and ERK, which work through mTORC1, a potent inhibitor of autophagy which is sensitive to rapamycin. (2) Vesicle expansion and completion of the autophagosome: this step requires the products of 2 ubiquitin-like conjugation systems that produce Atg5-Atg12 and Atg8/LC3-PE. (3) Finally, the mature autophagosome fuses with a lysosome through a step that involves proteins such as Rab7 and SNAREs. Rab GTPases that have been involved in the different steps of autophagy are indicated (in red). Abbreviations: Beclin1: BCL-2 interacting myosin/moesin-like coiled-coil protein 1; LC3: light chain 3 [Atg8 (yeast) is called LC3 in mammals]; mTORC1: mammalian target of rapamycin complex 1; PtdIns3P: phosphatidylinositol 3-phosphate; SNAREs: N-ethylmaleimide-sensitive factor attachment protein receptors; ULK1: UNC51-like kinase 1; WIPI: WD repeat domain phosphoinositide-interacting protein; p62: sequestosome 1; NBR1: neighbor of BRCA1 gene 1; OPTN: optineurin; LAMP2: lysosome-associated membrane protein 2.