Nephrin Signaling Results in Integrin
Animals
Cells, Cultured
Drosophila
/ cytology
Flow Cytometry
Gene Expression Regulation
/ genetics
Humans
Integrin beta1
/ metabolism
Membrane Proteins
/ genetics
Microscopy, Electron, Transmission
Phosphorylation
/ genetics
Podocytes
/ metabolism
Renal Insufficiency, Chronic
/ genetics
Signal Transduction
/ genetics
Statistics, Nonparametric
cytoskeleton
nephrin
renal cell biology
signaling
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
07
04
2018
accepted:
18
03
2019
pubmed:
18
5
2019
medline:
26
2
2020
entrez:
18
5
2019
Statut:
ppublish
Résumé
Patients with certain mutations in the gene encoding the slit diaphragm protein Nephrin fail to develop functional slit diaphragms and display severe proteinuria. Many adult-onset glomerulopathies also feature alterations in Nephrin expression and function. Nephrin signals from the podocyte slit diaphragm to the Actin cytoskeleton by recruiting proteins that can interact with C3G, a guanine nucleotide exchange factor of the small GTPase Rap1. Because Rap activity affects formation of focal adhesions, we hypothesized that Nephrin transmits signals to the Integrin receptor complex, which mediates podocyte adhesion to the extracellular matrix. To investigate Nephrin's role in transmitting signals to the Integrin receptor complex, we conducted genetic studies in Drosophila nephrocytes and validated findings from Drosophila in a cultured human podocyte model. Drosophila nephrocytes form a slit diaphragm-like filtration barrier and express the Nephrin ortholog Sticks and stones (Sns). A genetic screen identified Our findings suggest that Nephrin can mediate a signaling pathway that results in activation of Integrin
Sections du résumé
BACKGROUND
Patients with certain mutations in the gene encoding the slit diaphragm protein Nephrin fail to develop functional slit diaphragms and display severe proteinuria. Many adult-onset glomerulopathies also feature alterations in Nephrin expression and function. Nephrin signals from the podocyte slit diaphragm to the Actin cytoskeleton by recruiting proteins that can interact with C3G, a guanine nucleotide exchange factor of the small GTPase Rap1. Because Rap activity affects formation of focal adhesions, we hypothesized that Nephrin transmits signals to the Integrin receptor complex, which mediates podocyte adhesion to the extracellular matrix.
METHODS
To investigate Nephrin's role in transmitting signals to the Integrin receptor complex, we conducted genetic studies in Drosophila nephrocytes and validated findings from Drosophila in a cultured human podocyte model.
RESULTS
Drosophila nephrocytes form a slit diaphragm-like filtration barrier and express the Nephrin ortholog Sticks and stones (Sns). A genetic screen identified
CONCLUSIONS
Our findings suggest that Nephrin can mediate a signaling pathway that results in activation of Integrin
Identifiants
pubmed: 31097607
pii: ASN.2018040362
doi: 10.1681/ASN.2018040362
pmc: PMC6551783
doi:
Substances chimiques
Integrin beta1
0
Membrane Proteins
0
nephrin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1006-1019Informations de copyright
Copyright © 2019 by the American Society of Nephrology.
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