Inhibitory Effects of Robo2 on Nephrin: a Crosstalk Between Positive and Negative Signals Regulating Podocyte Structure

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2012 Jul 31

PMID 22840396

Citations 30

Authors

Xueping Fan

Qinggang Li

Anna Pisarek-Horowitz

Hila Milo Rasouly

Xiangling Wang

Ramon G Bonegio

Hang Wang

Margaret McLaughlin

Steve Mangos

Raghu Kalluri

Lawrence B Holzman

Iain A Drummond

Dennis Brown

David J Salant

Weining Lu

Affiliations

Soon will be listed here.

Abstract

Robo2 is the cell surface receptor for the repulsive guidance cue Slit and is involved in axon guidance and neuronal migration. Nephrin is a podocyte slit-diaphragm protein that functions in the kidney glomerular filtration barrier. Here, we report that Robo2 is expressed at the basal surface of mouse podocytes and colocalizes with nephrin. Biochemical studies indicate that Robo2 forms a complex with nephrin in the kidney through adaptor protein Nck. In contrast to the role of nephrin that promotes actin polymerization, Slit2-Robo2 signaling inhibits nephrin-induced actin polymerization. In addition, the amount of F-actin associated with nephrin is increased in Robo2 knockout mice that develop an altered podocyte foot process structure. Genetic interaction study further reveals that loss of Robo2 alleviates the abnormal podocyte structural phenotype in nephrin null mice. These results suggest that Robo2 signaling acts as a negative regulator on nephrin to influence podocyte foot process architecture.

Citing Articles

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