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• W2094517833 abstract "Spinocerebellar ataxia type 15 (SCA15) is a group of human neurodegenerative disorders characterized by a slowly progressing pure cerebellar ataxia. The inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1) is an intracellular IP3-induced Ca2+ release channel that was recently identified as a causative gene for SCA15. In most case studies, a heterozygous deletion of the IP3R1 gene was identified. However, one Japanese SCA15 family was found to have a Pro to Leu (P1059L) substitution in IP3R1. To investigate the effect of the P1059L mutation, we analyzed the channel properties of the mutant human IP3R1 by expressing it in an IP3R-deficient B lymphocyte cell line. The P1059L mutant was a functional Ca2+ release channel with a twofold higher IP3 binding affinity compared to wild-type IP3R1. The cooperative dependence of the Ca2+ release activity of the mutant on IP3 concentration was reduced, but both wild-type and mutant receptors produced similar B cell receptor-induced Ca2+ signals. These results demonstrate that the Ca2+ release properties of IP3R1 are largely unaffected by the P1059L mutation." @default.
• W2094517833 created "2016-06-24" @default.
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• W2094517833 date "2011-07-01" @default.
• W2094517833 modified "2023-10-03" @default.
• W2094517833 title "Functional characterization of the P1059L mutation in the inositol 1,4,5-trisphosphate receptor type 1 identified in a Japanese SCA15 family" @default.
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• W2094517833 doi "https://doi.org/10.1016/j.bbrc.2011.06.043" @default.
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