Functional Interaction of the Auxilin J Domain with the Nucleotide- and Substrate-binding Modules of Hsc70

Ungewickell, Ernst; Ungewickell, Huberta; Holstein, Susanne E. H.

doi:10.1074/jbc.272.31.19594

Cited by 72 publications

(88 citation statements)

References 45 publications

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“…Non-vertebrate species that have only one clathrin LC have a considerable range of sequence divergence. 3 However, for many of these, the most conserved sequence besides the HC-binding domain corresponds to the conserved LC sequence in vertebrates. Thus the function of the conserved sequence must be fundamental to clathrin function.…”

Section: Discussionmentioning

confidence: 99%

“…Most known regulatory and adaptor proteins influence coat assembly, membrane association, membrane fission, and uncoating by binding to sites on the HCs (1, 2), which themselves can self-assemble into a lattice. The LC subunits suppress spontaneous lattice assembly in vitro and thus allow cellular clathrin assembly to be controlled and subjected to regulation by additional proteins (3,4). Other roles for the LCs have not yet been clearly defined, despite the fact that LCs appear to be composed of multiple functional domains (5).…”

mentioning

confidence: 99%

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Huntingtin-interacting Protein 1 (Hip1) and Hip1-related Protein (Hip1R) Bind the Conserved Sequence of Clathrin Light Chains and Thereby Influence Clathrin Assembly in Vitro and Actin Distribution in Vivo

Chen

Brodsky

2005

Journal of Biological Chemistry

120

122

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Clathrin heavy and light chains form triskelia, which assemble into polyhedral coats of membrane vesicles that mediate transport for endocytosis and organelle biogenesis. Light chain subunits regulate clathrin assembly in vitro by suppressing spontaneous self-assembly of the heavy chains. The residues that play this regulatory role are at the N terminus of a conserved 22-amino acid sequence that is shared by all vertebrate light chains. Here we show that these regulatory residues and others in the conserved sequence mediate light chain interaction with Hip1 and Hip1R. These related proteins were previously found to be enriched in clathrin-coated vesicles and to promote clathrin assembly in vitro. We demonstrate Hip1R binding preference for light chains associated with clathrin heavy chain and show that Hip1R stimulation of clathrin assembly in vitro is blocked by mutations in the conserved sequence of light chains that abolish interaction with Hip1 and Hip1R. In vivo overexpression of a fragment of clathrin light chain comprising the Hip1R-binding region affected cellular actin distribution. Together these results suggest that the roles of Hip1 and Hip1R in affecting clathrin assembly and actin distribution are mediated by their interaction with the conserved sequence of clathrin light chains.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Huntingtin-interacting Protein 1 (Hip1) and Hip1-related Protein (Hip1R) Bind the Conserved Sequence of Clathrin Light Chains and Thereby Influence Clathrin Assembly in Vitro and Actin Distribution in Vivo

Chen

Brodsky

2005

Journal of Biological Chemistry

120

122

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“…Adaptor proteins such as AP-2, AP180, and epsin appear to mediate assembly through binding to the terminal domain of the CHC (7,9,13,28) and a model has been described in which these proteins cross-link the terminal domains of three independent triskelion bringing proximal and distal legs from adjacent CHCs into proximity (28,31). It is also well established that CLCs inhibit clathrin assembly in vitro (15,16). One model predicts that this occurs through the ability of CLCs to mask charge interactions needed for CHC self-interaction (22).…”

Section: Fig 2 Conserved Residues In Hip1 and Hip12/hip1r Are Necesmentioning

confidence: 99%

“…The starting material equals 1/10th of the amount of His 6 -CLCb added to the beads. influence is Ca 2ϩ , which at relatively high concentrations stimulates assembly (15). Ca 2ϩ binds to the CLC through an EFhand motif located between residues 85 and 96 and this induces a conformational change that affects CLC interaction with CHC (21).…”

Section: Fig 2 Conserved Residues In Hip1 and Hip12/hip1r Are Necesmentioning

confidence: 99%

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Huntingtin Interacting Protein 1 (HIP1) Regulates Clathrin Assembly through Direct Binding to the Regulatory Region of the Clathrin Light Chain

Legendre-Guillemin

Metzler

Lemaire

et al. 2005

Journal of Biological Chemistry

102

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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 clathrincoated 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.

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Two motifs within the tau microtubule‐binding domain mediate its association with the hsc70 molecular chaperone

Sarkar

Kuret

Lee

2008

J of Neuroscience Research

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Tau, a microtubule-associated protein with multiple phosphorylation sites, forms aggregates that correlate with neurodegeneration in Alzheimer Disease and several other neurodegenerative diseases, termed tauopathies. Hsc70 is a highly-expressed constitutive chaperone that can drive conformational change in proteins, prevent the aggregation of its substrates, recognize misfolded substrates, and facilitate their degradation. Here, we show that hsc70 binds to the microtubule-binding domain of tau in vitro and in vivo, without an absolute requirement for tau phosphorylation. Binding requires a carboxy-terminal region of hsc70 comprising its peptide-binding and variable domains. We have identified two hsc70-binding sites on tau and hydrophobic amino acids crucial for hsc70-binding. Interestingly, these hsc70-binding sites correspond to the β-structure elements that have been previously reported to facilitate tau aggregation. Thus, it is possible that hsc70 binding might directly inhibit tau-tau interactions that precede tau oligomerization and aggregation. Our results provide an important stimulus for research into how the hsc70-tau interaction might affect tau fate in normal cells and in disease.

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Functional Interaction of the Auxilin J Domain with the Nucleotide- and Substrate-binding Modules of Hsc70

Cited by 72 publications

References 45 publications

Huntingtin-interacting Protein 1 (Hip1) and Hip1-related Protein (Hip1R) Bind the Conserved Sequence of Clathrin Light Chains and Thereby Influence Clathrin Assembly in Vitro and Actin Distribution in Vivo

Huntingtin-interacting Protein 1 (Hip1) and Hip1-related Protein (Hip1R) Bind the Conserved Sequence of Clathrin Light Chains and Thereby Influence Clathrin Assembly in Vitro and Actin Distribution in Vivo

Huntingtin Interacting Protein 1 (HIP1) Regulates Clathrin Assembly through Direct Binding to the Regulatory Region of the Clathrin Light Chain

Two motifs within the tau microtubule‐binding domain mediate its association with the hsc70 molecular chaperone

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