Bartos, Katalin; Ramakrishnan, Suresh Krishna; Braga, Sophie; Hänzi, Barbara; Durussel, Fanny; Sridharan, Arjun Prakash; Zhu, Yao; Sheehan, David; Hynes, Nancy E.; Bonny, Olivier; Moor, Matthias B. (2020). Redox protein Memo 1 coordinates FGF23-driven signaling and small Rho-GTPases in the mouse kidney (In Press) (bioRxiv). Cold Spring Harbor Laboratory 10.1101/2020.12.04.402511
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2020.12.04.402511v2.full.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (1MB) | Preview |
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.
Item Type: |
Working Paper |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Protein- und Zellbiologie |
UniBE Contributor: |
Braga, Sophie Marie-Pierre |
Subjects: |
600 Technology > 610 Medicine & health |
Series: |
bioRxiv |
Publisher: |
Cold Spring Harbor Laboratory |
Language: |
English |
Submitter: |
Marla Rittiner |
Date Deposited: |
24 Jan 2022 14:27 |
Last Modified: |
05 Dec 2022 16:00 |
Publisher DOI: |
10.1101/2020.12.04.402511 |
BORIS DOI: |
10.48350/163472 |
URI: |
https://boris.unibe.ch/id/eprint/163472 |
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