Redox protein Memo 1 coordinates FGF23-driven signaling and small Rho-GTPases in the mouse kidney
Publisher DOI
Abstract
Memo promotes receptor tyrosine kinase (RTK) signaling by unknown mechanisms. Memo1 deletion in mice causes premature aging and unbalanced metabolism partially resembling Fgf23 and Klotho loss-of-function animals. Here, we report a role for Memo’s redox function in FGF23-driven RTK signaling in the kidney. Postnatally Memo-deficient (cKO) and floxed controls were treated with FGF23 or vehicle, followed by molecular and biochemical analyses. Findings were validated using cell culture and recombinant proteins. Memo cKO mice showed impaired renal ERK phosphorylation and transcriptional responses to FGF23. Redox proteomics revealed excessive thiols of Rho-GDP dissociation inhibitor 1 (Rho-GDI1). Renal RhoA abundance and activity were increased in Memo cKO. Immunoprecipitation analysis showed an association between Memo and Rho-GDI1. We confirmed an interaction between the two proteins, with Memo-dependent irreversible oxidation at Rho-GDI1 Cys79 in cell-free conditions. Collectively, our findings reveal that redox protein Memo promotes renal FGF23 signaling together with oxidative modulation of the Rho-GTPase network.
Date Issued
2020
Publication Type
Working Paper
Subject(s)
Language(s)
en
Author(s)
Bartos, Katalin | |
Ramakrishnan, Suresh Krishna | |
Hänzi, Barbara | |
Durussel, Fanny | |
Sridharan, Arjun Prakash | |
Zhu, Yao | |
Sheehan, David | |
Hynes, Nancy E. | |
Bonny, Olivier | |
Moor, Matthias B. |
Journal
bioRxiv
Publisher
Cold Spring Harbor Laboratory
Access(Rights)
Unknown