Role of IP3 Receptor in the Regulation of Synaptic Plasticity, Neuronal Function and Neuronal Development

2017 Fiscal Year Final Research Report

• Project/Area Number: 25221002
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Mikoshiba Katsuhiko 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, チームリーダー (30051840)
• Project Period (FY): 2013-05-31 – 2018-03-31
• Keywords: IP3受容体 / カルシウムイオン（Ca2+) / スパイン / シナプス可塑性 / 長期増強 / アストロサイト / IP3 / 神経回路

Outline of Final Research Achievements

IP3 receptor (IP3R)-deficient mice exhibit cerebellar ataxia, epileptic seizure-like symptom and retardation of neuronal development. However, it was a longstanding controversy if IP3R/Ca2+ signaling is involved in neuronal plasticity. We generated knock-out mice of all IP3R isoforms (IP3R1-3), and knock-out mice with region- or neuron-specific deletion of IP3R1. Mice lacking IP3R1 in Purkinje neurons demonstrated regulation of CaMKII/actin cytoskeleton/spine formation by IP3R1 (PNAS). LTP regulation by transport machines of IP3R1-coding mRNA (Nature Neurosci), modulatory roles of glial IP3R2 on gliotransmitter release to regulate neuronal functions (Nature Commun, J Clinical Invest), protein quality control by IP3R-associating ERp44 (Mol Cell) were also discovered. Much evidence, including GABA receptor regulation (Cell Rep) and apoptosis regulation by IP3R-bound IRBIT (eLIFE, PNAS), strongly indicates that IP3R controls synaptic plasticity.

Free Research Field

神経化学