Regulation of autophagy by the Rab GTPase network

Abstract

Autophagy (macroautophagy) is a highly conserved intracellular and lysosome-dependent degradation process in which autophagic substrates are enclosed and degraded by a double-membrane vesicular structure in a continuous and dynamic vesicle transport process. The Rab protein is a small GTPase that belongs to the Ras-like GTPase superfamily and regulates the vesicle traffic process. Numerous Rab proteins have been shown to be involved in various stages of autophagy. Rab1, Rab5, Rab7, Rab9A, Rab11, Rab23, Rab32, and Rab33B participate in autophagosome formation, whereas Rab9 is required in non-canonical autophagy. Rab7, Rab8B, and Rab24 have a key role in autophagosome maturation. Rab8A and Rab25 are also involved in autophagy, but their role is unknown. Here, we summarize new findings regarding the involvement of Rabs in autophagy and provide insights regarding future research on the mechanisms of autophagy regulation.

VPS9a Activates the Rab5 GTPase ARA7 to Confer Distinct Pre- and Postinvasive Plant Innate Immunity

“…As for MVBs, Rab5 GTPases are essential for autophagosome formation. These double membrane structures could mediate the secretion of membrane material to the encasement as an alternative pathway (Ao et al, 2014). However, from previous investigations, loss of autophagy leads to increased powdery mildew resistance, rather than susceptibility, which is the opposite effect of the vps9a-2 mutant .…”

Simultaneous inhibition of the ubiquitin-proteasome system and autophagy enhances apoptosis induced by ER stress aggravators in human pancreatic cancer cells

“…(H) Panc-1 cells were pretreated with Rap (100 nM) for 30 min, followed by treatment with 2.5 mM WA or 10 mM CQ for another 24 h, and then the indicated protein levels were analyzed by western blot. marker), RAB7 (late endosome marker), RAB11 (recycling endosome marker), and LAMP1 are critical for lysosome fusion with endosomes and autophagosomes, 27 we examined the effects of WA on the expression of these proteins by western blot analysis. Interestingly, treating cells with WA increased the levels of RAB5 and RAB7 in a dose-dependent manner (Fig.…”

Autophagy in Cardiac Development

“…Currently, the core machinery for autophagosome maturation is not completely understood. However, many molecules directly involved in this process have been identified, including soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) proteins (Guo et al 2014, Takáts et al 2014, Endosomal sorting required for transport (ESCRT) proteins (Rusten & Stenmark 2009), the Homotypic fusion and protein sorting (HOPS) complex (Moreau et al 2011, Jiang et al 2014 and Rab GTPase (Chua et al 2011, Ao et al 2014). In addition, some other proteins such as VCP (VCP/p97), a member of the AAA+-ATPase family of chaperone-like proteins, and SNAPIN, an adaptor protein in SNARE complex have also recently been uncovered to have essential roles in autophagosome maturation (Shi et al 2016, Tresse et al 2010.…”