Title |
The GTPase-Activating Protein GRAF1 Regulates the CLIC/GEEC Endocytic Pathway
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Published in |
Current Biology, November 2008
|
DOI | 10.1016/j.cub.2008.10.044 |
Pubmed ID | |
Authors |
Richard Lundmark, Gary J. Doherty, Mark T. Howes, Katia Cortese, Yvonne Vallis, Robert G. Parton, Harvey T. McMahon |
Abstract |
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. |
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Researcher | 38 | 16% |
Student > Master | 23 | 9% |
Student > Bachelor | 17 | 7% |
Professor > Associate Professor | 12 | 5% |
Other | 38 | 16% |
Unknown | 32 | 13% |
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Neuroscience | 6 | 2% |
Other | 28 | 11% |
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