The membrane-remodeling PX-BAR protein SNX18 is required for autophagy
(English)Manuscript (preprint) (Other academic)
Autophagy is a catabolic pathway targeting cytoplasmic material for lysosomal degradation,thereby protecting cells from accumulation of toxic components and enabling cells to survivescarce nutrient supplies. Macroautophagy is characterized by the sequestration of cytoplasmicmaterial into double-membrane vesicles, but the membrane remodeling events required forformation of autophagic vesicles are still not completely understood. However, the class IIIphosphatidylinositol 3-kinase (PI3K)/Vps34 complex and phosphatidylinositol-3-phosphate(PI3P) are of core importance to induction of autophagy. Since PX domain containingproteins are known to bind PI3P and other phosphoinositides and mediate membraneremodeling and trafficking events, we performed an imaging-based siRNA screen targetingPX domain proteins using formation of GFP-LC3 positive autophagosomes as a read-out.The PX-BAR protein SNX18 was found to strongly inhibit autophagosome formation. In linewith this, overexpression of SNX18 increased LC3 lipidation and GFP-LC3 spot formationand we demonstrate that membrane binding of SNX18 is required for efficientautophagosome formation. Moreover, SNX18 colocalizes and interacts with the autophagyassociatedproteins LC3 and TBK1. Our study identified the PX-BAR protein SNX18 to beinvolved in membrane events required for autophagosome formation.
Cell and Molecular Biology
Research subject Medical Biochemistry
IdentifiersURN: urn:nbn:se:umu:diva-51967OAI: oai:DiVA.org:umu-51967DiVA: diva2:490623