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

Knævelsrud, Helene (author)

Søreng, Kristiane (author)

Raiborg, Camilla (author)

Håberg, Karin (author): Umeå universitet,Institutionen för medicinsk kemi och biofysik

Rasmuson, Fredrik (author): Umeå universitet,Institutionen för medicinsk kemi och biofysik

Brech, Andreas (author)

Liestøl, Knut (author)

Rusten, Tor Erik (author)

Stenmark, Harald (author)

Neufeld, Thomas P (author)

Carlsson, Sven R (author): Umeå universitet,Institutionen för medicinsk kemi och biofysik

Simonsen, Anne (author)

(creator_code:org_t)

2013-07-22
2013
English.
In: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 202:2, s. 331-349

Related links:: https://umu.diva-por... (primary) (Raw object); show more...; http://jcb.rupress.o...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Knævelsrud, Hele ...; Søreng, Kristian ...; Raiborg, Camilla; Håberg, Karin; Rasmuson, Fredri ...; Brech, Andreas; show more...; Liestøl, Knut; Rusten, Tor Erik; Stenmark, Harald; Neufeld, Thomas ...; Carlsson, Sven R; Simonsen, Anne; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

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