Linked Life Data

12393793

Source:http://linkedlifedata.com/resource/pubmed/id/12393793

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pubmed-article:12393793pubmed:abstractTextHuntington disease (HD) is caused by polyglutamine [poly(Q)] expansion in the protein huntingtin (htt). Although the exact mechanism of disease progression remains to be elucidated, altered interactions of mutant htt with its protein partners could contribute to the disease. Using the yeast two-hybrid system, we have isolated a novel htt interacting protein, HIP14. HIP14's interaction with htt is inversely correlated to the poly(Q) length in htt. mRNAs of 9 and 6 bp are transcribed from the HIP14 gene, with the 6 kb transcript being predominantly expressed in the brain. HIP14 protein is enriched in the brain, shows partial co-localization with htt in the striatum, and is found in medium spiny projection neurons, the subset of neurons affected in HD. HIP14 localizes to the Golgi, and to vesicles in the cytoplasm. The HIP14 protein has sequence similarity to Akr1p, a protein essential for endocytosis in Saccharomyces cerevisiae. Expression of human HIP14 results in rescue of the temperature-sensitive lethality in akr1 Delta yeast cells and, furthermore, restores their defect in endocytosis, demonstrating a role for HIP14 in intracellular trafficking. Our findings suggest that decreased interaction between htt and HIP14 could contribute to the neuronal dysfunction in HD by perturbing normal intracellular transport pathways in neurons.lld:pubmed
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pubmed-article:12393793pubmed:articleTitleHIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis.lld:pubmed
pubmed-article:12393793pubmed:affiliationCentre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.lld:pubmed
pubmed-article:12393793pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:12393793pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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