title: Aftiphilin is a component of the clathrin machinery in neurons.
abstract: Aftiphilin was identified through a database search for proteins containing binding motifs for the gamma-ear domain of clathrin adaptor protein 1 (AP-1). Here, we demonstrate that aftiphilin is expressed predominantly in brain where it is enriched on clathrin-coated vesicles. In addition to eight gamma-ear-binding motifs, aftiphilin contains two WXXF-acidic motifs that mediate binding to the alpha-ear of clathrin adaptor protein 2 (AP-2) and three FXXFXXF/L motifs that mediate binding to the alpha- and beta2-ear. We demonstrate that aftiphilin uses these motifs for interactions with AP-1 and AP-2 and that it immunoprecipitates these APs but not AP-3 or AP-4 from brain extracts. Aftiphilin demonstrates a brefeldin A sensitive localization to the trans-Golgi network in hippocampal neurons where it co-localizes with AP-1. Aftiphilin is also found at synapses where it co-localizes with synaptophysin and AP-2. Our data suggest a role for aftiphilin in clathrin-mediated trafficking in neurons.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Que., Canada H3A 2B4.
authors.forename: Jonathon L
authors.initials: JL
authors.lastname: Burman
authors.forename: Sylwia
authors.initials: S
authors.lastname: Wasiak
authors.forename: Brigitte
authors.initials: B
authors.lastname: Ritter
authors.forename: Elaine
authors.initials: E
authors.lastname: de Heuvel
authors.forename: Peter S
authors.initials: PS
authors.lastname: McPherson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002966:Clathrin / Q000502:physiology*; D017077:Culture Media, Conditioned; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017386:Sequence Homology, Amino Acid
chemical_list: C500389:Aftph protein, rat; D002352:Carrier Proteins; D002966:Clathrin; D017077:Culture Media, Conditioned; D009419:Nerve Tissue Proteins