title: Endophilin marks and controls a clathrin-independent endocytic pathway.
abstract: Endocytosis is required for internalization of micronutrients and turnover of membrane components. Endophilin has been assigned as a component of clathrin-mediated endocytosis. Here we show in mammalian cells that endophilin marks and controls a fast-acting tubulovesicular endocytic pathway that is independent of AP2 and clathrin, activated upon ligand binding to cargo receptors, inhibited by inhibitors of dynamin, Rac, phosphatidylinositol-3-OH kinase, PAK1 and actin polymerization, and activated upon Cdc42 inhibition. This pathway is prominent at the leading edges of cells where phosphatidylinositol-3,4-bisphosphate-produced by the dephosphorylation of phosphatidylinositol-3,4,5-triphosphate by SHIP1 and SHIP2-recruits lamellipodin, which in turn engages endophilin. This pathway mediates the ligand-triggered uptake of several G-protein-coupled receptors such as α2a- and β1-adrenergic, dopaminergic D3 and D4 receptors and muscarinic acetylcholine receptor 4, the receptor tyrosine kinases EGFR, HGFR, VEGFR, PDGFR, NGFR and IGF1R, as well as interleukin-2 receptor. We call this new endocytic route fast endophilin-mediated endocytosis (FEME).
authors.affiliation: 1] MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK [2] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Boucrot
authors.affiliation: Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK.
authors.forename: Antonio P A
authors.initials: AP
authors.lastname: Ferreira
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Almeida-Souza
authors.affiliation: 1] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK [2] Department of Biology, Ecole Normale Supérieure de Cachan, 94235 Cachan, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Debard
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Vallis
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Howard
authors.affiliation: Institut Pasteur, Unité de Pathogenie Moleculaire Microbienne, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Bertot
authors.affiliation: Institut Pasteur, Unité de Pathogenie Moleculaire Microbienne, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sauvonnet
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Harvey T
authors.initials: HT
authors.lastname: McMahon
mesh_terms: D000199:Actins / Q000378:metabolism; D000217:Acyltransferases / Q000378:metabolism*; D002460:Cell Line; D002966:Clathrin; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D008024:Ligands; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D000199:Actins; D002966:Clathrin; D008024:Ligands; D018129:Phosphatidylinositol Phosphates; D043562:Receptors, G-Protein-Coupled; D015375:Receptors, Interleukin-2; C060980:phosphatidylinositol 3,4-diphosphate; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase; D020794:Receptor Protein-Tyrosine Kinases; D034281:Dynamins