The role of MAGI-2 in maintenance of slit-diaphragm

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02823
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Chiba University
• Principal Investigator: ASANUMA KATSUHIKO 千葉大学, 大学院医学研究院, 教授 (60449064)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 慢性腎臓病 / 蛋白尿 / ポドサイト / スリット膜

Outline of Final Research Achievements

We focused on the role of Membrane-associated guanylate kinase inverted 2 (MAGI-2) to investigate the mechanisms that orchestrate the localization of SD associated proteins. We found that MAGI-2 downregulation coincides with a reduced expression of SD associated proteins in a human kidney , and that a podocyte-specific deficiency of MAGI-2 in mice derogates the localization of Nephrin and Neph1. Although a deficiency of zonula occuldens-1 (ZO-1) downregulated the endogenous Neph1 expression, MAGI-2 recovered the Neph1 expression at the cellular edge in cultured mouse podocytes. Futhermore, overexpression of MAGI-2 preserved Nephrin localization on cell-cell contacts. Thus, the localization of Nephrin and Neph1 in intercellular junctions is regulated mainly via the PDZ domains of MAGI-2 together with other scaffold proteins. In summary, MAGI-2 stabilizes the localization of SD backbone proteins via its PDZ domain.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

今回の研究で、血清蛋白の最終濾過障壁であるスリット膜の維持にMAGI-2が重要な働きを果たしていることがわかった。また、ヒト腎疾患でMAGI-2の発現が低下していることから、MAGI-2の発現を制御することが、慢性腎臓病に対する新いターゲットになることが判明した。