Molecular mechanism of Na+/Ca2+ exchanger regulation in renal distal tubules

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07302
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Fukuoka University
• Principal Investigator: Iwamoto Takahiro 福岡大学, 医学部, 教授 (20300973)
• Co-Investigator(Kenkyū-buntansha): 喜多 知 福岡大学, 医学部, 講師 (50797107)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: イオン輸送体 / 遠位尿細管 / Ca2+再吸収 / Ca2+シグナル / 遺伝子改変マウス

Outline of Final Research Achievements

Na+/Ca2+ exchanger type 1 (NCX1) is abundantly expressed on the basolateral membrane of the distal tubule and is thought to be involved in renal Ca2+ reabsorption. However, the localization mechanism of NCX1 to the basolateral membrane and the regulation mechanism of transport by hormones and physiologically active substances have not been fully elucidated. In this study, we generated MDCK cells transfected with an NCX1 mutant with abnormal membrane localization and its knock-in and transgenic mice, and experimentally found that the localization of NCX1 to the basolateral membrane is regulated by various receptor stimuli, leading to the modulation of Ca2+ reabsorption.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

1型Na+/Ca2+交換輸送体（NCX1）は、細胞膜を介して3個のNa+と1個のCa2+を交換輸送する重要なCa2+トランスポーター（輸送担体）であり、Ca2+ホメオスタシス（恒常性）の維持やCa2+シグナルの形成に関わっている。本研究では、遠位尿細管基底側膜へのNCX1発現局在が各種受容体刺激により調節され、腎臓のCa2+再吸収が制御されることをin vitro & in vivo実験系により実証した。本研究の成果により、Ca2+代謝異常症（高Ca血症、低Ca血症）に関する病因・病態の解明が進むとともに、新規治療法の開発に繋がることが期待される。