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Science 328 (5983): 1281-1284

Copyright © 2010 by the American Association for the Advancement of Science

FCHo Proteins Are Nucleators of Clathrin-Mediated Endocytosis

William Mike Henne,*,{dagger} Emmanuel Boucrot,{dagger},{ddagger} Michael Meinecke, Emma Evergren, Yvonne Vallis, Rohit Mittal, Harvey T. McMahon{ddagger}

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.

Medical Research Council, Laboratory of Molecular Biology (MRC-LMB), Hills Road, Cambridge CB2 0QH, UK.

* Present address: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.

{dagger} These authors contributed equally to this work.

{ddagger} To whom correspondence should be addressed. E-mail: hmm{at}mrc-lmb.cam.ac.uk (H.T.M); eboucrot{at}mrc-lmb.cam.ac.uk (E.B.)


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