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

EMBO J. 1997 May 1;16(9):2240-50. doi: 10.1093/emboj/16.9.2240.


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 types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Protein Complex 1*
  • Adaptor Protein Complex 2*
  • Adaptor Protein Complex 3*
  • Adaptor Protein Complex mu Subunits*
  • Adaptor Proteins, Vesicular Transport
  • Alanine / metabolism
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cattle
  • Clathrin / metabolism*
  • Endocytosis*
  • Glycoproteins*
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins*
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism*
  • Phosphatidylinositols / metabolism
  • Phosphoproteins / metabolism*
  • Protein Conformation
  • Protein Sorting Signals / metabolism*
  • Tyrosine / metabolism


  • AP3M2 protein, human
  • Adaptor Protein Complex 1
  • Adaptor Protein Complex 2
  • Adaptor Protein Complex 3
  • Adaptor Protein Complex mu Subunits
  • Adaptor Proteins, Vesicular Transport
  • Clathrin
  • Glycoproteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Phosphatidylinositols
  • Phosphoproteins
  • Protein Sorting Signals
  • adaptor protein complex 1, mu 2 subunit
  • adaptor protein complex 2, mu 2 subunit
  • Tyrosine
  • Alanine