HAP1 facilitates effects of mutant huntingtin on inositol 1,4,5-trisphosphate-induced Ca2+ release in primary culture of striatal medium spiny neurons
Tang, Tie-Shan and Tu, Huiping and Orban, Paul C and Chan, Edmond Y W and Hayden, Michael R and Bezprozvanny, Ilya (2004) HAP1 facilitates effects of mutant huntingtin on inositol 1,4,5-trisphosphate-induced Ca2+ release in primary culture of striatal medium spiny neurons. European Journal of Neuroscience, 20 (7). 1779–1787. ISSN 0953-816X (https://doi.org/10.1111/j.1460-9568.2004.03633.x)
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Huntington's disease is caused by polyglutamine expansion (exp) in huntingtin (Htt). Htt-associated protein-1 (HAP1) was the first identified Htt-binding partner. The type 1 inositol (1,4,5)-trisphosphate receptor (InsP3R1) is an intracellular Ca2+ release channel that plays an important role in neuronal function. Recently, we identified a InsP3R1-HAP1A-Htt ternary complex in the brain and demonstrated that Httexp, but not normal Htt, activates InsP3R1 in bilayers and facilitates InsP3R1-mediated intracellular Ca2+ release in medium spiny striatal neurons [MSN; T.-S. Tang et al. (2003) Neuron, 39, 227-239]. Here we took advantage of mice with targeted disruption of both HAP1 alleles (HAP1 -/-) to investigate the role of HAP1 in functional interactions between Htt and InsP3R1. We determined that: (i) HAP1 is expressed in the MSN; (ii) HAP1A facilitates functional effects of Htt and Htt(exp) on InsP3R1 in planar lipid bilayers; (iii) HAP1 is required for changes in MSN basal Ca2+ levels resulting from Htt or Htt(exp) overexpression; (iv) HAP1 facilitates potentiation of InsP3R1-mediated Ca2+ release by Htt(exp) in mouse MSN. Our present results indicate that HAP1 plays an important role in functional interactions between Htt and InsP3R1.
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Item type: Article ID code: 49547 Dates: DateEventOctober 2004Published14 September 2004Published OnlineKeywords: animals, calcium, cells, cultured, corpus striatum, huntington disease, inositol 1,4,5-trisphosphate receptors, kinetics, lipid bilayers, membrane glycoproteins, membrane transport proteins, methoxyhydroxyphenylglycol, mice, mice, knockout, nerve tissue proteins, neurons, serotonin plasma membrane transport proteins, Pharmacy and materia medica, Neuroscience. Biological psychiatry. Neuropsychiatry, Neuroscience(all) Subjects: Medicine > Pharmacy and materia medica
Medicine > Internal medicine > Neuroscience. Biological psychiatry. NeuropsychiatryDepartment: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 03 Oct 2014 12:11 Last modified: 22 May 2023 03:16 URI: https://strathprints.strath.ac.uk/id/eprint/49547