Disease-associated mutations in inositol 1,4,5-trisphosphate receptor subunits impair channel function.

ABSTRACT: The inositol 1,4,5-trisphosphate (IP₃) receptors (IP₃Rs), which form tetrameric channels, play pivotal roles in regulating the spatiotemporal patterns of intracellular calcium signals. Mutations in IP₃Rs have been increasingly associated with many debilitating human diseases such as ataxia, Gillespie syndrome, and generalized anhidrosis. However, how these mutations affect IP₃R function, and how the perturbation of as-sociated calcium signals contribute to the pathogenesis and severity of these diseases remains largely uncharacterized. Moreover, many of these diseases occur as the result of autosomal dominant inheritance, suggesting that WT and mutant subunits associate in heterotetrameric channels. How the in-corporation of different numbers of

SUBMITTER: Terry LE 

PROVIDER: S-EPMC7939385 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature