Proteomics

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ATG9A is a component of the ESCRT system and governs plasma membrane repair

ABSTRACT: ATG9 is often described as the sole transmembrane protein among the core autophagy factors. The mammalian ATG9A is notorious for trafficking through numerous cellular compartments including the plasma membrane. The reasons for ATG9As wide intracellular distribution and its role at the PM are not fully understood. Here we show that ATG9A intimately interacts with components of the ESCRT system. Employing proteomic analyses with APEX2-ATG9A we identified a number of ESCRTs as ATG9A interactors, including TSG101 and ALIX, and uncovered cooperation between ATG9A and ESCRTs in protection against PM damage. ATG9A knockouts sensitized PM to permeabilization by a broad spectrum of agents including gasdermin and Mycobacterium tuberculosis. ESCRTs phenocopied ATG9A in protection against PM injury. Thus, in addition to its function in autophagy, ATG9A is a component of the ESCRT system engaged in the repair of PM

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo

SUBMITTER: Vojo Deretic  

PROVIDER: MSV000084519 | MassIVE | Wed Oct 30 18:13:00 GMT 2019

SECONDARY ACCESSION(S): PXD016084

REPOSITORIES: MassIVE

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The integral membrane protein ATG9A plays a key role in autophagy. It displays a broad intracellular distribution and is present in numerous compartments, including the plasma membrane (PM). The reasons for the distribution of ATG9A to the PM and its role at the PM are not understood. Here, we show that ATG9A organizes, in concert with IQGAP1, components of the ESCRT system and uncover cooperation between ATG9A, IQGAP1 and ESCRTs in protection from PM damage. ESCRTs and ATG9A phenocopied each ot  ...[more]

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