title: Huntingtin interacting protein 1 (HIP1) regulates clathrin assembly through direct binding to the regulatory region of the clathrin light chain.
abstract: Huntingtin interacting protein 1 (HIP1) is a component of clathrin coats. We previously demonstrated that HIP1 promotes clathrin assembly through its central helical domain, which binds directly to clathrin light chains (CLCs). To better understand the relationship between CLC binding and clathrin assembly we sought to dissect this interaction. Using C-terminal deletion constructs of the HIP1 helical domain, we identified a region between residues 450 and 456 that is required for CLC binding. Within this region, point mutations showed the importance of residues Leu-451, Leu-452, and Arg-453. Mutants that fail to bind CLC are unable to promote clathrin assembly in vitro but still mediate HIP1 homodimerization and heterodimerization with the family member HIP12/HIP1R. Moreover, HIP1 binding to CLC is necessary for HIP1 targeting to clathrin-coated pits and clathrin-coated vesicles. Interestingly, HIP1 binds to a highly conserved region of CLC previously demonstrated to regulate clathrin assembly. These results suggest a role for HIP1/CLC interactions in the regulation of clathrin assembly.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 rue University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Legendre-Guillemin
authors.forename: Martina
authors.initials: M
authors.lastname: Metzler
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Lemaire
authors.forename: Jacynthe
authors.initials: J
authors.lastname: Philie
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Peter S
authors.initials: PS
authors.lastname: McPherson
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D033941:Clathrin Light Chains / Q000737:chemistry* / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D006816:Huntington Disease; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D051381:Rats; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D033941:Clathrin Light Chains; D004268:DNA-Binding Proteins