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. 1997 May 1;16(9):2240–2250. doi: 10.1093/emboj/16.9.2240

Regulatory interactions in the recognition of endocytic sorting signals by AP-2 complexes.

I Rapoport 1, M Miyazaki 1, W Boll 1, B Duckworth 1, L C Cantley 1, S Shoelson 1, T Kirchhausen 1
PMCID: PMC1169826  PMID: 9171339

Abstract

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 mu2 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.

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Selected References

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