The GTPase-activating protein GRAF1 regulates the CLIC/GEEC endocytic pathway

Lundmark, Richard (author): Umeå universitet,Institutionen för medicinsk kemi och biofysik

Doherty, Gary J (author)

Howes, Mark T (author)

Cortese, Katia (author)

Vallis, Yvonne (author)

Parton, Robert G (author)

McMahon, Harvey T (author)

(creator_code:org_t)

Elsevier BV, 2008
2008
English.
In: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 18:22, s. 1802-1808

Related links:: http://www.cell.com/...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Lundmark, Richar ...; Doherty, Gary J; Howes, Mark T; Cortese, Katia; Vallis, Yvonne; Parton, Robert G; show more...; McMahon, Harvey ...; show less...

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