Regulatory interactions in the recognition of endocytic sorting signals by AP-2 complexes Academic Article uri icon


MeSH Major

  • Adaptor Protein Complex 1
  • Adaptor Protein Complex 2
  • Adaptor Protein Complex 3
  • Adaptor Protein Complex mu Subunits
  • Clathrin
  • Endocytosis
  • Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Protein Sorting Signals


  • 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.

publication date

  • May 1997



  • Academic Article



  • eng

PubMed Central ID

  • PMC1169826

Digital Object Identifier (DOI)

  • 10.1093/emboj/16.9.2240

PubMed ID

  • 9171339

Additional Document Info

start page

  • 2240

end page

  • 50


  • 16


  • 9