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Regulatory interactions in the recognition of endocytic sorting signals by AP‐2 complexes
Author(s) -
Rapoport Iris,
Miyazaki Masaya,
Boll Werner,
Duckworth Brian,
Cantley Lewis C.,
Shoelson Steve,
Kirchhausen Tomas
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.9.2240
Subject(s) - biology , clathrin , endocytic cycle , clathrin adaptor proteins , signal transducing adaptor protein , microbiology and biotechnology , endocytosis , tyrosine , protein subunit , phosphorylation , biochemistry , cooperativity , inositol , receptor , gene
Many plasma membrane proteins destined for endocytosis are concentrated into clathrin‐coated pits through the recognition of a tyrosine‐based motif in their cytosolic domains by an adaptor (AP‐2) complex. The μ2 subunit of isolated AP‐2 complexes binds specifically, but rather weakly, to proteins bearing the tyrosine‐based signal. We now demonstrate, using peptides with a photoreactive probe, that this binding is strengthened significantly when the AP‐2 complex is present in clathrin coats, indicating that there is cooperativity between receptor–AP‐2 interactions and coat formation. Phosphoinositides with a phosphate at the D‐3 position of the inositol ring, but not other isomers, also increase the affinity of the AP‐2 complex for the tyrosine‐based motif. AP‐2 is the first protein known (in any context) to interact with phosphatidylinositol 3‐phosphate. Our findings indicate that receptor recruitment can be coupled to clathrin coat assembly and suggest a mechanism for regulation of membrane traffic by lipid products of phosphoinositide 3‐kinases.