title: GRAF1-dependent endocytosis.
abstract: The role of endocytosis in controlling a multitude of cell biological events is well established. Molecular and mechanistic characterization of endocytosis has predominantly focused on CME (clathrin-mediated endocytosis), although many other endocytic pathways have been described. It was recently shown that the BAR (Bin/amphiphysin/Rvs) and Rho GAP (GTPase-activating protein) domain-containing protein GRAF1 (GTPase regulator associated with focal adhesion kinase-1) is found on prevalent, pleiomorphic endocytic membranes, and is essential for the major, clathrin-independent endocytic pathway that these membranes mediate. This pathway is characterized by its ability to internalize GPI (glycosylphosphatidylinositol)-anchored proteins, bacterial toxins and large amounts of extracellular fluid. These membrane carriers are highly dynamic and associated with the activity of the small G-protein Cdc42 (cell division cycle 42). In the present paper, we review the role of GRAF1 in this CLIC (clathrin-independent carrier)/GEEC (GPI-anchored protein-enriched early endocytic compartment) endocytic pathway and discuss the current understanding regarding how this multidomain protein functions at the interface between membrane sculpting, small G-protein signalling and endocytosis.
authors.affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK. richard.lundmark@medchem.umu.se
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Doherty
authors.forename: Richard
authors.initials: R
authors.lastname: Lundmark
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D015398:Signal Transduction / Q000502:physiology
chemical_list: D020690:GTPase-Activating Proteins; D017261:Glycosylphosphatidylinositols; D026901:Membrane Transport Proteins; D051417:Focal Adhesion Kinase 1; D019204:GTP-Binding Proteins