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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Protein Complex 2 / metabolism
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport / metabolism
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Animals
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Calcium-Binding Proteins / metabolism
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Cell Line
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Cell Membrane / metabolism
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Cells, Cultured
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Clathrin / metabolism*
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Clathrin-Coated Vesicles / metabolism*
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Endocytosis*
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Fatty Acid-Binding Proteins
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HeLa Cells
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism
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Membrane Proteins
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Mice
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Models, Molecular
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Neurons / cytology
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Neurons / metabolism
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Phosphoproteins / metabolism
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Protein Multimerization
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Protein Structure, Tertiary
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Proteins / chemistry
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Proteins / metabolism*
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RNA Interference
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Rats
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Rats, Sprague-Dawley
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Recombinant Fusion Proteins / metabolism
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Synaptic Vesicles / metabolism
Substances
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Adaptor Protein Complex 2
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Calcium-Binding Proteins
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Clathrin
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EPS15 protein, human
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FCHO1 protein, human
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Fatty Acid-Binding Proteins
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Fcho2 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Phosphoproteins
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Proteins
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Recombinant Fusion Proteins
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intersectin 1