PortalPublikationenThe Rho-GTPase binding protein IQGAP2 is required for the gl...

The Rho-GTPase binding protein IQGAP2 is required for the glomerular filtration barrier

Standard

The Rho-GTPase binding protein IQGAP2 is required for the glomerular filtration barrier. / Sugano, Yuya; Lindenmeyer, Maja T; Auberger, Ines; Ziegler, Urs; Segerer, Stephan; Cohen, Clemens D; Neuhauss, Stephan C F; Loffing, Johannes.

in: KIDNEY INT, Jahrgang 88, Nr. 5, 11.2015, S. 1047-56.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Sugano, Y, Lindenmeyer, MT, Auberger, I, Ziegler, U, Segerer, S, Cohen, CD, Neuhauss, SCF & Loffing, J 2015, 'The Rho-GTPase binding protein IQGAP2 is required for the glomerular filtration barrier', KIDNEY INT, Jg. 88, Nr. 5, S. 1047-56. https://doi.org/10.1038/ki.2015.197

APA

Sugano, Y., Lindenmeyer, M. T., Auberger, I., Ziegler, U., Segerer, S., Cohen, C. D., Neuhauss, S. C. F., & Loffing, J. (2015). The Rho-GTPase binding protein IQGAP2 is required for the glomerular filtration barrier. KIDNEY INT, 88(5), 1047-56. https://doi.org/10.1038/ki.2015.197

Vancouver

Sugano Y, Lindenmeyer MT, Auberger I, Ziegler U, Segerer S, Cohen CD et al. The Rho-GTPase binding protein IQGAP2 is required for the glomerular filtration barrier. KIDNEY INT. 2015 Nov;88(5):1047-56. https://doi.org/10.1038/ki.2015.197

Bibtex

@article{e6df5ae5ffdc42db9885bc0d9c069c35,
title = "The Rho-GTPase binding protein IQGAP2 is required for the glomerular filtration barrier",
abstract = "Podocyte dysfunction impairs the size selectivity of the glomerular filter, leading to proteinuria, hypoalbuminuria, and edema, clinically defined as nephrotic syndrome. Hereditary forms of nephrotic syndrome are linked to mutations in podocyte-specific genes. To identify genes contributing to podocyte dysfunction in acquired nephrotic syndrome, we studied human glomerular gene expression data sets for glomerular-enriched gene transcripts differentially regulated between pretransplant biopsy samples and biopsies from patients with nephrotic syndrome. Candidate genes were screened by in situ hybridization for expression in the zebrafish pronephros, an easy-to-use in vivo assay system to assess podocyte function. One glomerulus-enriched product was the Rho-GTPase binding protein, IQGAP2. Immunohistochemistry found a strong presence of IQGAP2 in normal human and zebrafish podocytes. In zebrafish larvae, morpholino-based knockdown of iqgap2 caused a mild foot process effacement of zebrafish podocytes and a cystic dilation of the urinary space of Bowman's capsule upon onset of urinary filtration. Moreover, the glomerulus of zebrafish morphants showed a glomerular permeability for injected high-molecular-weight dextrans, indicating an impaired size selectivity of the glomerular filter. Thus, IQGAP2 is a Rho-GTPase binding protein, highly abundant in human and zebrafish podocytes, which controls normal podocyte structure and function as evidenced in the zebrafish pronephros. ",
keywords = "Animals, Bowman Capsule, GTPase-Activating Proteins, Gene Knockdown Techniques, Humans, In Situ Hybridization, Kidney Glomerulus, Nephrotic Syndrome, Podocytes, Pronephros, Zebrafish, Zebrafish Proteins, ras GTPase-Activating Proteins, Journal Article, Research Support, Non-U.S. Gov't",
author = "Yuya Sugano and Lindenmeyer, {Maja T} and Ines Auberger and Urs Ziegler and Stephan Segerer and Cohen, {Clemens D} and Neuhauss, {Stephan C F} and Johannes Loffing",
year = "2015",
month = nov,
doi = "10.1038/ki.2015.197",
language = "English",
volume = "88",
pages = "1047--56",
journal = "KIDNEY INT",
issn = "0085-2538",
publisher = "NATURE PUBLISHING GROUP",
number = "5",

}

RIS

TY - JOUR

T1 - The Rho-GTPase binding protein IQGAP2 is required for the glomerular filtration barrier

AU - Sugano, Yuya

AU - Lindenmeyer, Maja T

AU - Auberger, Ines

AU - Ziegler, Urs

AU - Segerer, Stephan

AU - Cohen, Clemens D

AU - Neuhauss, Stephan C F

AU - Loffing, Johannes

PY - 2015/11

Y1 - 2015/11

N2 - Podocyte dysfunction impairs the size selectivity of the glomerular filter, leading to proteinuria, hypoalbuminuria, and edema, clinically defined as nephrotic syndrome. Hereditary forms of nephrotic syndrome are linked to mutations in podocyte-specific genes. To identify genes contributing to podocyte dysfunction in acquired nephrotic syndrome, we studied human glomerular gene expression data sets for glomerular-enriched gene transcripts differentially regulated between pretransplant biopsy samples and biopsies from patients with nephrotic syndrome. Candidate genes were screened by in situ hybridization for expression in the zebrafish pronephros, an easy-to-use in vivo assay system to assess podocyte function. One glomerulus-enriched product was the Rho-GTPase binding protein, IQGAP2. Immunohistochemistry found a strong presence of IQGAP2 in normal human and zebrafish podocytes. In zebrafish larvae, morpholino-based knockdown of iqgap2 caused a mild foot process effacement of zebrafish podocytes and a cystic dilation of the urinary space of Bowman's capsule upon onset of urinary filtration. Moreover, the glomerulus of zebrafish morphants showed a glomerular permeability for injected high-molecular-weight dextrans, indicating an impaired size selectivity of the glomerular filter. Thus, IQGAP2 is a Rho-GTPase binding protein, highly abundant in human and zebrafish podocytes, which controls normal podocyte structure and function as evidenced in the zebrafish pronephros.

AB - Podocyte dysfunction impairs the size selectivity of the glomerular filter, leading to proteinuria, hypoalbuminuria, and edema, clinically defined as nephrotic syndrome. Hereditary forms of nephrotic syndrome are linked to mutations in podocyte-specific genes. To identify genes contributing to podocyte dysfunction in acquired nephrotic syndrome, we studied human glomerular gene expression data sets for glomerular-enriched gene transcripts differentially regulated between pretransplant biopsy samples and biopsies from patients with nephrotic syndrome. Candidate genes were screened by in situ hybridization for expression in the zebrafish pronephros, an easy-to-use in vivo assay system to assess podocyte function. One glomerulus-enriched product was the Rho-GTPase binding protein, IQGAP2. Immunohistochemistry found a strong presence of IQGAP2 in normal human and zebrafish podocytes. In zebrafish larvae, morpholino-based knockdown of iqgap2 caused a mild foot process effacement of zebrafish podocytes and a cystic dilation of the urinary space of Bowman's capsule upon onset of urinary filtration. Moreover, the glomerulus of zebrafish morphants showed a glomerular permeability for injected high-molecular-weight dextrans, indicating an impaired size selectivity of the glomerular filter. Thus, IQGAP2 is a Rho-GTPase binding protein, highly abundant in human and zebrafish podocytes, which controls normal podocyte structure and function as evidenced in the zebrafish pronephros.

KW - Animals

KW - Bowman Capsule

KW - GTPase-Activating Proteins

KW - Gene Knockdown Techniques

KW - Humans

KW - In Situ Hybridization

KW - Kidney Glomerulus

KW - Nephrotic Syndrome

KW - Podocytes

KW - Pronephros

KW - Zebrafish

KW - Zebrafish Proteins

KW - ras GTPase-Activating Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ki.2015.197

DO - 10.1038/ki.2015.197

M3 - SCORING: Journal article

C2 - 26154927

VL - 88

SP - 1047

EP - 1056

JO - KIDNEY INT

JF - KIDNEY INT

SN - 0085-2538

IS - 5

ER -