The TBC/RabGAP Armus Coordinates Rac1 and Rab7 Functions during Autophagy

Bernadette Carroll, Noor Mohd-Naim, Filipe Maximiano, Marieke A. Frasa, Jessica McCormack, Mattea Finelli, Sigrid B. Thoresen, Louis Perdios, Reiko Daigaku, Richard E. Francis, Clare Futter, Ivan Dikic, Vania M.M. Braga*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

55 Citations (Scopus)

Abstract

Autophagy is an evolutionarily conserved process that enables catabolic and degradative pathways. These pathways commonly depend on vesicular transport controlled by Rabs, small GTPases inactivated by TBC/RabGAPs. The Rac1 effector TBC/RabGAP Armus (TBC1D2A) is known to inhibit Rab7, a key regulator of lysosomal function. However, the precise coordination of signaling and intracellular trafficking that regulates autophagy is poorly understood. We find that overexpression of Armus induces the accumulation of enlarged autophagosomes, while Armus depletion significantly delays autophagic flux. Upon starvation-induced autophagy, Rab7 is transiently activated. This spatiotemporal regulation of Rab7 guanosine triphosphate/guanosine diphosphate cycling occurs by Armus recruitment to autophagosomes via interaction with LC3, a core autophagy regulator. Interestingly, autophagy potently inactivates Rac1. Active Rac1 competes with LC3 for interaction with Armus and thus prevents its appropriate recruitment to autophagosomes. The precise coordination between Rac1 and Rab7 activities during starvation suggests that Armus integrates autophagy with signaling and endocytic trafficking.

Original languageEnglish
Pages (from-to)15-28
Number of pages14
JournalDevelopmental Cell
Volume25
Issue number1
DOIs
Publication statusPublished - 15 Apr 2013

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