Rab7b modulates autophagic flux by interacting with Atg4B |
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| Authors: | Ingrid Kjos Marita Borg Distefano Frank Sætre Urska Repnik Petter Holland Arwyn T Jones Nikolai Engedal Anne Simonsen Oddmund Bakke Cinzia Progida |
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| Institution: | 1. Department of Biosciences, University of Oslo, Oslo, Norway;2. Centre for Immune Regulation, University of Oslo, Oslo, Norway;3. Centre for Molecular Medicine Norway, University of Oslo, Oslo, Norway;4. Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway;5. Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Wales, UK |
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| Abstract: | Autophagy (macroautophagy) is a highly conserved eukaryotic degradation pathway in which cytosolic components and organelles are sequestered by specialized autophagic membranes and degraded through the lysosomal system. The autophagic pathway maintains basal cellular homeostasis and helps cells adapt during stress; thus, defects in autophagy can cause detrimental effects. It is therefore crucial that autophagy is properly regulated. In this study, we show that the cysteine protease Atg4B, a key enzyme in autophagy that cleaves LC3, is an interactor of the small GTPase Rab7b. Indeed, Atg4B interacts and co‐localizes with Rab7b on vesicles. Depletion of Rab7b increases autophagic flux as indicated by the increased size of autophagic structures as well as the magnitude of macroautophagic sequestration and degradation. Importantly, we demonstrate that Rab7b regulates LC3 processing by modulating Atg4B activity. Taken together, our findings reveal Rab7b as a novel negative regulator of autophagy through its interaction with Atg4B. |
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| Keywords: | Atg4B autophagy LC3 Rab GTPases Rab7b |
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