Membrane remodeling by the PX-BAR protein SNX18 promotes autophagosome formation

Helene Knævelsrud, Kristiane Søreng, Camilla Raiborg, Karin Håberg, Fredrik Rasmuson, Andreas Brech, Knut Liestøl, Tor Erik Rusten, Harald Stenmark, Thomas P. Neufeld, Sven R. Carlsson, Anne Simonsen

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

The membrane remodeling events required for autophagosome biogenesis are still poorly understood. Because PX domain proteins mediate membrane remodeling and trafficking, we conducted an imaging based siRNA screen for autophagosome formation targeting human PX proteins. The PX-BAR protein SNX18 was identified as a positive regulator of autophagosome formation, and its Drosophila melanogaster homologue SH3 PX1 was found to be required for efficient autophagosome formation in the larval fat body. We show that SNX18 is required for recruitment of Atg16L1-positive recycling endosomes to a perinuclear area and for delivery of Atg16L1- and LC3-positive membranes to autophagosome precursors. We identify a direct interaction of SNX18 with LC3 and show that the pro-autophagic activity of SNX18 depends on its membrane binding and tubulation capacity. We also show that the function of SNX18 in membrane tubulation and autophagy is negatively regulated by phosphorylation of S233. We conclude that SNX18 promotes autophagosome formation by virtue of its ability to remodel membranes and provide membrane to forming autophagosomes.

Original languageEnglish (US)
Pages (from-to)331-349
Number of pages19
JournalJournal of Cell Biology
Volume202
Issue number2
DOIs
StatePublished - Jul 2013

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