title: FCHo proteins are nucleators of clathrin-mediated endocytosis.
abstract: Clathrin-mediated endocytosis, the major pathway for ligand internalization into eukaryotic cells, is thought to be initiated by the clustering of clathrin and adaptors around receptors destined for internalization. However, here we report that the membrane-sculpting F-BAR domain-containing Fer/Cip4 homology domain-only proteins 1 and 2 (FCHo1/2) were required for plasma membrane clathrin-coated vesicle (CCV) budding and marked sites of CCV formation. Changes in FCHo1/2 expression levels correlated directly with numbers of CCV budding events, ligand endocytosis, and synaptic vesicle marker recycling. FCHo1/2 proteins bound specifically to the plasma membrane and recruited the scaffold proteins eps15 and intersectin, which in turn engaged the adaptor complex AP2. The FCHo F-BAR membrane-bending activity was required, leading to the proposal that FCHo1/2 sculpt the initial bud site and recruit the clathrin machinery for CCV formation.
authors.affiliation: Medical Research Council, Laboratory of Molecular Biology (MRC-LMB), Hills Road, Cambridge CB2 0QH, UK.
authors.forename: William Mike
authors.initials: WM
authors.lastname: Henne
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Boucrot
authors.forename: Michael
authors.initials: M
authors.lastname: Meinecke
authors.forename: Emma
authors.initials: E
authors.lastname: Evergren
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Vallis
authors.forename: Rohit
authors.initials: R
authors.lastname: Mittal
authors.forename: Harvey T
authors.initials: HT
authors.lastname: McMahon
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000378:metabolism*; D004705:Endocytosis; D050556:Fatty Acid-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008958:Models, Molecular; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: D033962:Adaptor Protein Complex 2; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D002135:Calcium-Binding Proteins; D002966:Clathrin; C486206:EPS15 protein, human; C524557:FCHO1 protein, human; D050556:Fatty Acid-Binding Proteins; C497032:Fcho2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C115919:intersectin 1
references.citation: Structure. 2007 Jul;15(7):839-52
references.pmid: 17540576
references.citation: Exp Cell Res. 2006 Dec 10;312(20):4036-48
references.pmid: 17097636
references.citation: Science. 2004 Jan 23;303(5657):495-9
references.pmid: 14645856
references.citation: J Cell Biol. 2003 Sep 1;162(5):909-18
references.pmid: 12952941
references.citation: Curr Biol. 2009 Dec 15;19(23):1979-87
references.pmid: 19962315
references.citation: Science. 2001 Feb 9;291(5506):1051-5
references.pmid: 11161218
references.citation: Nat Rev Mol Cell Biol. 2009 Sep;10(9):583-96
references.pmid: 19696796
references.citation: J Biol Chem. 2003 Nov 21;278(47):46772-81
references.pmid: 12952949
references.citation: J Biol Chem. 2007 Sep 7;282(36):26481-9
references.pmid: 17626015
references.citation: Dev Cell. 2006 Jun;10(6):839-50
references.pmid: 16740485
references.citation: Science. 2002 May 3;296(5569):913-6
references.pmid: 11988576
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3833-8
references.pmid: 15007177
references.citation: Nature. 2007 Aug 23;448(7156):883-8
references.pmid: 17713526
references.citation: Cell. 2007 May 18;129(4):761-72
references.pmid: 17512409
references.citation: Blood. 2006 Apr 15;107(8):3350-8
references.pmid: 16397132
references.citation: Mol Biol Cell. 2009 Nov;20(22):4640-51
references.pmid: 19776351
references.citation: Cell. 2008 Mar 7;132(5):807-17
references.pmid: 18329367
references.citation: Cell. 2002 May 17;109(4):523-35
references.pmid: 12086608
references.citation: EMBO J. 2009 Oct 21;28(20):3103-16
references.pmid: 19713939