title: Interactions of annexins with the mu subunits of the clathrin assembly proteins.
abstract: A number of biochemical and genetic studies have suggested that certain annexins play important roles in the endocytic pathway, possibly involving the generation, localization, or fusion of endocytic compartments. In a yeast two-hybrid screen for proteins that interact with the N-terminal domain of annexin A2 we identified the mu2 subunit of the clathrin assembly protein complex AP-2. The interaction depended upon two copies of a Yxx phi amino acid sequence motif (Y = tyrosine, x = variable residue, phi = bulky, hydrophobic residue) in the annexin that is also characteristic of the binding site for mu2 on the cytoplasmic domains of transmembrane receptors. The interaction between mu2 and full-length annexin A2 was demonstrated in vitro to be direct, to require calcium, and to be functional in the sense that annexin A2 was able to recruit the mu2 to immobilized lipids. Examination of other annexins and mu subunits demonstrated that annexin A2 also binds the mu1 subunit of the AP-1 complex, that annexin A6 binds mu1 and mu2, and that annexin A1 binds only mu1. We propose that annexins can "masquerade" as transmembrane receptors when they are attached to membranes in the presence of calcium and that they might therefore function to initiate calcium-regulated coated pit formation at the cell surface or on intracellular organelles.
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA. Creutz@virginia.edu
authors.forename: Carl E
authors.initials: CE
authors.lastname: Creutz
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Snyder
mesh_terms: D000595:Amino Acid Sequence; D017302:Annexins / Q000378:metabolism*; D001483:Base Sequence; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D020798:Two-Hybrid System Techniques
chemical_list: D017302:Annexins; D002966:Clathrin