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Synaptopodin Is a Coincidence Detector of Tyrosine versus Serine/Threonine Phosphorylation for the Modulation of Rho Protein Crosstalk in Podocytes

Authors
 Lisa Buvall  ;  Hanna Wallentin  ;  Jonas Sieber  ;  Svetlana Andreeva  ;  Hoon Young Choi  ;  Peter Mundel  ;  Anna Greka 
Citation
 JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol.28(3) : 837-851, 2017 
Journal Title
 JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 
ISSN
 1046-6673 
Issue Date
2017
MeSH
Animals ; Calcineurin/metabolism ; Cells, Cultured ; Mice ; Microfilament Proteins/physiology* ; Phosphorylation ; Podocytes/physiology* ; Receptor Cross-Talk ; Serine/metabolism* ; Signal Transduction ; Threonine/metabolism* ; Tyrosine/metabolism* ; rhoA GTP-Binding Protein/physiology*
Keywords
EGFR ; FSGS ; Rac1 ; TRPC5 ; cytoskeleton ; glomerular disease
Abstract
Tyrosine and serine/threonine signal-transduction pathways influence many aspects of cell behavior, including the spatial and temporal regulation of the actin cytoskeleton. However, little is known about how input from diverse tyrosine and serine/threonine kinases is integrated to control Rho protein crosstalk and actin remodeling, which are critically important in podocyte health and disease. Here we unveil the proteolytically-regulated, actin organizing protein synaptopodin as a coincidence detector of tyrosine versus serine/threonine phosphorylation. We show that serine/threonine and tyrosine kinases duel for synaptopodin stability versus degradation. EGFR/Src-mediated tyrosine phosphorylation of synaptopodin in podocytes promotes binding to the serine/threonine phosphatase calcineurin. This leads to the loss of 14-3-3 binding, resulting in synaptopodin degradation, Vav2 activation, enhanced Rac1 signaling, and ultimate loss of stress fibers. Our studies reveal how synaptopodin, a single proteolytically-controlled protein, integrates antagonistic tyrosine versus serine/threonine phosphorylation events for the dynamic control of the actin cytoskeleton in podocytes.
Full Text
http://jasn.asnjournals.org/content/28/3/837.long
DOI
10.1681/ASN.2016040414
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Choi, Hoon Young(최훈영) ORCID logo https://orcid.org/0000-0002-4245-0339
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154722
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