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Identification of a family of endocytic proteins that define a new α‐adaptin ear‐binding motif
Author(s) -
Ritter Brigitte,
Philie Jacynthe,
Girard Martine,
Tung Elaine C,
Blondeau Francois,
McPherson Peter S
Publication year - 2003
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400004
Subject(s) - endocytic cycle , clathrin , endocytosis , clathrin adaptor proteins , microbiology and biotechnology , internalization , biology , signal transducing adaptor protein , protein subunit , sequence motif , genetics , signal transduction , receptor , gene
Endocytosis by clathrin‐coated vesicles (CCVs) is an important mechanism mediating protein internalization. Here, we show that two proteins identified through a proteomics analysis of CCVs are new components of the endocytic machinery. The proteins, named NECAP (adaptin‐ear‐binding coat‐associated protein) 1 and 2, are paralogues that display no sequence similarity or common domains with any known protein. Both are enriched in CCV coats, and further analysis of the brain‐enriched isoform, NECAP 1, shows its partial localization to clathrin‐coated pits and direct binding to the globular ear domain of the α‐adaptin subunit (α‐ear) of the adaptor protein 2 (AP‐2) complex. Intriguingly, this interaction is mediated by a new motif, WVQF, that uses a distinct α‐ear interface relative to known α‐ear‐binding partners. Disruption of this interaction blocks clathrin‐mediated endocytosis. Together, our studies identify a new family of endocytic proteins that define a unique AP‐2‐binding motif.