Roles of the pH regulation through HCO3- transporters in perisynaptic astrocytes

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07068
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Showa Pharmaceutical University
• Principal Investigator: MIZUTANI Akihiro 昭和薬科大学, 薬学部, 教授 (30242861)
• Research Collaborator: KAWAAI katsuhiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: NBCe1

Outline of Final Research Achievements

We found that a catalytic subunit of calcineurin binds to the C terminus of NBCe1-C in the mouse cerebellum. Heterologous-coexpression experiments revealed that calcineurin binds to NBCe1-C via a “PQIRIE” motif at its C terminus. The interaction enhanced cell surface expression of NBCe1-C, resulting in an increase of its transporter activity, for which the phosphatase activity of calcineurin was essential. When NBCe1-C was stably expressed in HeLa cells, its cell surface expression was enhanced by an intracellular Ca2+ concentration increase and was suppressed by FK506, a specific inhibitor of calcineurin. These mechanisms of surface expression and transport activity of NBCe1-C regulated by the Ca2+-CaM-calcineurin axis indicate specialized functions of NBCe1-C in the brain.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

SLC4A4遺伝子、その欠損により精神遅滞を引き起こすこと、また、その発現量と自殺行動との関係が示唆されている。今回の発見は、シナプスを包囲するアストロサイト突起に発現するNBCe1/C（中枢神経系特異的SLAC4A4j発現産物）の細胞膜発現が、Ca2+シグナル依存的に調節されること示したのである。この発見により、スナプス間隙のpH環境が、神経伝達の状況によってアストロサイトが調節しうる可能性と、SLC4A4が果たす高次脳機能における分子メカニズムの一端が明らかになった。