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

First Author  Knævelsrud H Year  2013
Journal  J Cell Biol Volume  202
Issue  2 Pages  331-49
PubMed ID  23878278 Mgi Jnum  J:201640
Mgi Id  MGI:5514491 Doi  10.1083/jcb.201205129
Citation  Knaevelsrud H, et al. (2013) Membrane remodeling by the PX-BAR protein SNX18 promotes autophagosome formation. J Cell Biol 202(2):331-49
abstractText  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.
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