A heterodimeric SNX4:SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly

Zuri Anton, Virginie M S Betin, Boris Simonetti, Colin J Traer, Naomi Attar, Peter J Cullen, Jon D Lane*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

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Abstract

The sorting nexins (SNXs) are a family of peripheral membrane proteins that direct protein trafficking decisions within the endocytic network. Emerging evidence in yeast and mammalian cells implicates a sub-group of SNXs in selective and non-selective forms of (macro)autophagy. Using siRNA and CRISPR-Cas9, we demonstrate that the SNX-BAR protein, SNX4, is needed for efficient LC3 lipidation and autophagosome assembly in mammalian cells. SNX-BARs exist as homo- and heterodimers, and we show that SNX4 forms functional heterodimers with either SNX7 or SNX30 that associate with tubulovesicular endocytic membranes. Detailed image-based analysis during the early stages of autophagosome assembly reveal that SNX4:SNX7 is the autophagy-specific SNX-BAR heterodimer, required for efficient recruitment/retention of core autophagy regulators at the nascent isolation membrane. SNX4 partially co-localises with juxtanuclear ATG9A-positive membranes, with our data linking the SNX4 autophagy defect to the mis-trafficking and/or retention of ATG9A in the Golgi region. Together, our findings show that the SNX4:SNX7 heterodimer coordinates ATG9A trafficking within the endocytic network to establish productive autophagosome assembly sites, thus extending knowledge of SNXs as positive regulators of autophagy.
Original languageEnglish
Article numberjcs246306
Number of pages38
JournalJournal of Cell Science
Volume133
Issue number14
DOIs
Publication statusPublished - 15 Jul 2020

Keywords

  • sorting nexin
  • SNX4
  • SNX7
  • SNX30
  • endosomes
  • autophagy
  • ATG9A

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