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The GTPase-activating protein GRAF1 regulates the CLIC/GEEC endocytic pathway
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2008 (English)In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 18, no 22, 1802-1808 p.Article in journal (Refereed) Published
Abstract [en]

Clathrin-independent endocytosis is an umbrella term for a variety of endocytic pathways that internalize numerous cargoes independently of the canonical coat protein Clathrin [1, 2]. Electron-microscopy studies have defined the pleiomorphic CLathrin-Independent Carriers (CLICs) and GPI-Enriched Endocytic Compartments (GEECs) as related major players in such uptake [3, 4]. This CLIC/GEEC pathway relies upon cellular signaling and activation through small G proteins, but mechanistic insight into the biogenesis of its tubular and tubulovesicular carriers is lacking. Here we show that the Rho-GAP-domain-containing protein GRAF1 marks, and is indispensable for, a major Clathrin-independent endocytic pathway. This pathway is characterized by its ability to internalize bacterial exotoxins, GPI-linked proteins, and extracellular fluid. We show that GRAF1 localizes to PtdIns(4,5)P2-enriched, tubular, and punctate lipid structures via N-terminal BAR and PH domains. These membrane carriers are relatively devoid of caveolin1 and flotillin1 but are associated with activity of the small G protein Cdc42. This study provides the first specific noncargo marker for CLIC/GEEC endocytic membranes and demonstrates how GRAF1 can coordinate small G protein signaling and membrane remodeling to facilitate internalization of CLIC/GEEC pathway cargoes.

Place, publisher, year, edition, pages
2008. Vol. 18, no 22, 1802-1808 p.
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URN: urn:nbn:se:umu:diva-42779DOI: 10.1016/j.cub.2008.10.044PubMedID: 19036340OAI: diva2:410374
Available from: 2011-04-13 Created: 2011-04-13 Last updated: 2011-04-13Bibliographically approved

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Lundmark, Richard
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