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Science. 2010 Jun 4;328(5983):1281-4. doi: 10.1126/science.1188462. Epub 2010 May 6.

FCHo proteins are nucleators of clathrin-mediated endocytosis.

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1
Medical Research Council, Laboratory of Molecular Biology (MRC-LMB), Hills Road, Cambridge CB2 0QH, UK.

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.

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PMID:
20448150
PMCID:
PMC2883440
DOI:
10.1126/science.1188462
[Indexed for MEDLINE]
Free PMC Article

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