Abstract
Cell–matrix adhesion is crucial for maintaining the mechanical integrity of epithelial tissues. Podocytes—a key component of the glomerular filtration barrier—are exposed to permanent transcapillary filtration pressure and must therefore adhere tightly to the underlying glomerular basement membrane (GBM). The major cell–matrix adhesion receptor in podocytes is the integrin α3β1, which connects laminin 521 in the GBM through various adaptor proteins to the intracellular actin cytoskeleton. Other cell–matrix adhesion receptors expressed by podocytes include the integrins α2β1 and αvβ3, α-dystroglycan, syndecan-4 and type XVII collagen. Mutations in genes encoding any of the components critical for podocyte adhesion cause glomerular disease. This Review highlights recent advances in our understanding of the cell biology and genetics of podocyte adhesion with special emphasis on glomerular disease.
Key Points
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Podocytes are constantly exposed to mechanical stress; therefore, strong adhesion of podocytes to the glomerular basement membrane (GBM) is required for blood ultrafiltration
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Podocyte adhesions to the GBM are mediated by transmembrane receptors, such as integrin α3β1, which link extracellular GBM proteins to the intracellular cytoskeleton
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Mutations in components that mediate podocyte–matrix adhesions may cause glomerular disease characterized by GBM abnormalities, podocyte foot process effacement, and proteinuria
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Glomerular disease caused by defective podocyte adhesion might be ameliorated by drugs that decrease transcapillary filtration pressure
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Work in the authors' laboratory is supported by grants from the Dutch Kidney Foundation and the Dutch Cancer Society.
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N. Sachs researched data for the article, contributed substantially to the discussion of content and wrote the article. A. Sonnenberg contributed substantially to the discussion of content, and reviewed/edited the manuscript before submission.
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Sachs, N., Sonnenberg, A. Cell–matrix adhesion of podocytes in physiology and disease. Nat Rev Nephrol 9, 200–210 (2013). https://doi.org/10.1038/nrneph.2012.291
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DOI: https://doi.org/10.1038/nrneph.2012.291
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