Vinculin is required to maintain glomerular barrier integrity

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Albuminuria / genetics
  • Albuminuria / metabolism
  • Animals
  • Cell Movement
  • Cell Surface Extensions / metabolism
  • Cell Surface Extensions / pathology
  • Cells, Cultured
  • Focal Adhesion Kinase 1 / metabolism
  • Focal Adhesions / metabolism
  • Focal Adhesions / pathology
  • Glomerulonephritis, Membranous / metabolism*
  • Glomerulonephritis, Membranous / pathology
  • Glomerulosclerosis, Focal Segmental / metabolism*
  • Glomerulosclerosis, Focal Segmental / pathology
  • Mechanotransduction, Cellular
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nephrosis, Lipoid / metabolism*
  • Nephrosis, Lipoid / pathology
  • Phosphorylation
  • Podocytes / metabolism*
  • Podocytes / pathology
  • Vinculin / deficiency
  • Vinculin / genetics
  • Vinculin / metabolism*
  • Zonula Occludens-1 Protein / metabolism


  • Tjp1 protein, mouse
  • VCL protein, human
  • Zonula Occludens-1 Protein
  • Vinculin
  • Focal Adhesion Kinase 1
  • Ptk2 protein, mouse