Aberrant IP₃ receptor activities revealed by comprehensive analysis of pathological mutations causing spinocerebellar ataxia 29.

ABSTRACT: Spinocerebellar ataxia type 29 (SCA29) is autosomal dominant congenital ataxia characterized by early-onset motor delay, hypotonia, and gait ataxia. Recently, heterozygous missense mutations in an intracellular Ca²⁺ channel, inositol 1,4,5-trisphosphate (IP₃) receptor type 1 (IP₃R1), were identified as a cause of SCA29. However, the functional impacts of these mutations remain largely unknown. Here, we determined the molecular mechanisms by which pathological mutations affect IP₃R1 activity and Ca²⁺ dynamics. Ca²⁺ imaging using IP₃R-null HeLa cells generated by genome editing revealed that all SCA29 mutations identified within or near the IP₃-binding domain of IP₃R1 completely abolished chann

SUBMITTER: Ando H 

PROVIDER: S-EPMC6275503 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature