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Kidney Int. 2018 Mar;93(3):643-655. doi: 10.1016/j.kint.2017.09.021. Epub 2017 Dec 12.

Vinculin is required to maintain glomerular barrier integrity.

Author information

1
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
2
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
3
Department of Medicine/Cardiology, University of California, San Diego, School of Medicine, La Jolla, California, USA and Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
4
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Veterans Affairs Hospital, Nashville, Tennessee, USA.
5
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. Electronic address: Christoph.Ballestrem@manchester.ac.uk.
6
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; School of Biology, Faculty of Biology, Medicine and Health, University of Medicine, Manchester Academic Health Science Centre, UK. Electronic address: Rachel.Lennon@manchester.ac.uk.
7
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address: shuta.ishibe@yale.edu.

Abstract

Cell-matrix interactions and podocyte intercellular junctions are key for maintaining the glomerular filtration barrier. Vinculin, a cytoplasmic protein, couples actin filaments to integrin-mediated cell-matrix adhesions and to cadherin-based intercellular junctions. Here, we examined the role of vinculin in podocytes by the generation of a podocyte-specific knockout mouse. Mice lacking podocyte vinculin had increased albuminuria and foot process effacement following injury in vivo. Analysis of primary podocytes isolated from the mutant mice revealed defects in cell protrusions, altered focal adhesion size and signaling, as well as impaired cell migration. Furthermore, we found a marked mislocalization of the intercellular junction protein zonula occludens-1. In kidney sections from patients with focal segmental glomerulosclerosis, minimal change disease and membranous nephropathy, we observed dramatic differences in the expression levels and localization of vinculin. Thus, our results suggest that vinculin is necessary to maintain the integrity of the glomerular filtration barrier by modulating podocyte foot processes and stabilizing intercellular junctions.

KEYWORDS:

cell adhesion; glomerular disease; glomerular filtration barrier; podocyte; vinculin

PMID:
29241625
PMCID:
PMC5846847
DOI:
10.1016/j.kint.2017.09.021
[Indexed for MEDLINE]
Free PMC Article

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