The role of MAGI-2 in maintenance of slit-diaphragm
Description: 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.
Amount: ¥17,290,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (B)
Start date: 2018-04-01
End date: 2021-03-31
Investigator: KATSUHIKO ASANUMA
Institution: Chiba University
Funded outputs count: 14
Funder award ID: 18H02823
OpenAlex ID: G6853936776