Analysis of the relationship between abnormal organella and spinocerebellar ataxia 15

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06761
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Hisatsune Chihiro 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (10321803)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: cerebellum / calcium

Outline of Final Research Achievements

Spinocerebellar ataxia (SCA) is one of the neural disorders, which represents malfunction and degeneration of the cerebellum and the brain stem. IP3R1 is one of the causal gene for SCA, but the mechanism by which IP3R1 causes SCA is unknown. Using the brain specific IP3R1 conditional KO mice, we found that Purkinje cells (PCs) lacking IP3R1 exhibit the decrease of the expression of Calbindin, a Ca2+ binding protein.
On the other hand, we also analyzed the functional effect of a novel mutation in SCA29 patients we found. The mutation localized at the suppressor region of IP3R1, which inhibits IP3 binding to IP3R1. We found that the IP3R1 mutation significantly increased the IP3 binding affinity to the receptor and enhanced Ca2+ release from the endoplasmic reticulum. The mutation drastically changed the property of the intracellular Ca2+ signal from a transient to a sigmoidal pattern, suggesting that the altered Ca2+ homeostasis in PCs is one of the pathogenesis of SCA29.

Free Research Field

Molecular neurobiology