title: Actin binding by Hip1 (huntingtin-interacting protein 1) and Hip1R (Hip1-related protein) is regulated by clathrin light chain.
abstract: The huntingtin-interacting protein family members (Hip1 and Hip1R in mammals and Sla2p in yeast) link clathrin-mediated membrane traffic to actin cytoskeleton dynamics. Genetic data in yeast have implicated the light chain subunit of clathrin in regulating this link. To test this hypothesis, the biophysical properties of mammalian Hip1 and Hip1R and their interaction with clathrin light chain and actin were analyzed. The coiled-coil domains (clathrin light chain-binding) of Hip1 and Hip1R were found to be stable homodimers with no propensity to heterodimerize in vitro. Homodimers were also predominant in vivo, accounting for cellular segregation of Hip1 and Hip1R functions. Coiled-coil domains of Hip1 and Hip1R differed in their stability and flexibility, correlating with slightly different affinities for clathrin light chain and more markedly with effects of clathrin light chain binding on Hip protein-actin interactions. Clathrin light chain binding induced a compact conformation of both Hip1 and Hip1R and significantly reduced actin binding by their THATCH domains. Thus, clathrin is a negative regulator of Hip-actin interactions. These observations necessarily change models proposed for Hip protein function.
authors.affiliation: Graduate Program in Biophysics, University of California, San Francisco, California 94143-0552, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Wilbur
authors.forename: Chih-Ying
authors.initials: CY
authors.lastname: Chen
authors.forename: Venus
authors.initials: V
authors.lastname: Manalo
authors.forename: Peter K
authors.initials: PK
authors.lastname: Hwang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fletterick
authors.forename: Frances M
authors.initials: FM
authors.lastname: Brodsky
mesh_terms: D000199:Actins / Q000737:chemistry*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002966:Clathrin / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D004926:Escherichia coli / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins; D008954:Models, Biological; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002966:Clathrin; D004268:DNA-Binding Proteins; C073368:HIP1 protein, human; C489537:HIP1R protein, human; D008840:Microfilament Proteins; D033921:Vesicular Transport Proteins
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