title: Membrane remodeling by the PX-BAR protein SNX18 promotes autophagosome formation.
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 SH3PX1 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.
authors.affiliation: Institute of Basic Medical Sciences, University of Oslo, 0316 Oslo, Norway. helene.knavelsrud@ibv.uio.no
authors.forename: Helene
authors.initials: H
authors.lastname: Knævelsrud
authors.forename: Kristiane
authors.initials: K
authors.lastname: Søreng
authors.forename: Camilla
authors.initials: C
authors.lastname: Raiborg
authors.forename: Karin
authors.initials: K
authors.lastname: Håberg
authors.forename: Fredrik
authors.initials: F
authors.lastname: Rasmuson
authors.forename: Andreas
authors.initials: A
authors.lastname: Brech
authors.forename: Knut
authors.initials: K
authors.lastname: Liestøl
authors.forename: Tor Erik
authors.initials: TE
authors.lastname: Rusten
authors.forename: Harald
authors.initials: H
authors.lastname: Stenmark
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Neufeld
authors.forename: Sven R
authors.initials: SR
authors.lastname: Carlsson
authors.forename: Anne
authors.initials: A
authors.lastname: Simonsen
mesh_terms: D000818:Animals; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005216:Fat Body / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007814:Larva / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism*; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D021381:Protein Transport; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism*
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C498519:SH3PX1 protein, Drosophila; C530791:SNX18 protein, human; D058305:Sorting Nexins