FCHo proteins are nucleators of clathrin-mediated endocytosis.
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.
Henne
William Mike
WM
Medical Research Council, Laboratory of Molecular Biology (MRC-LMB), Hills Road, Cambridge CB2 0QH, UK.
Boucrot
Emmanuel
E
Meinecke
Michael
M
Evergren
Emma
E
Vallis
Yvonne
Y
Mittal
Rohit
R
McMahon
Harvey T
HT
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
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
Structure. 2007 Jul;15(7):839-52
17540576
Exp Cell Res. 2006 Dec 10;312(20):4036-48
17097636
Science. 2004 Jan 23;303(5657):495-9
14645856
J Cell Biol. 2003 Sep 1;162(5):909-18
12952941
Curr Biol. 2009 Dec 15;19(23):1979-87
19962315
Science. 2001 Feb 9;291(5506):1051-5
11161218
Nat Rev Mol Cell Biol. 2009 Sep;10(9):583-96
19696796
J Biol Chem. 2003 Nov 21;278(47):46772-81
12952949
J Biol Chem. 2007 Sep 7;282(36):26481-9
17626015
Dev Cell. 2006 Jun;10(6):839-50
16740485
Science. 2002 May 3;296(5569):913-6
11988576
Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3833-8
15007177
Nature. 2007 Aug 23;448(7156):883-8
17713526
Cell. 2007 May 18;129(4):761-72
17512409
Blood. 2006 Apr 15;107(8):3350-8
16397132
Mol Biol Cell. 2009 Nov;20(22):4640-51
19776351
Cell. 2008 Mar 7;132(5):807-17
18329367
Cell. 2002 May 17;109(4):523-35
12086608
EMBO J. 2009 Oct 21;28(20):3103-16
19713939