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The podocyte cytoskeleton—key to a functioning glomerulus in health and disease

Abstract

Almost all mammalian cell types have morphologies that are uniquely tailored to their physiological functions. This immense variation in cell shape depends on an underlying network of dynamic and interconnected actin and microtubule polymers. The glomerular podocyte is an archetypal example of such specialization, with a complex cytoskeleton underlying its delicate architectural features. Dynamic control of this cytoskeletal matrix seems to center around the slit diaphragm, a complex of proteins at the cell–cell junction between adjacent podocyte foot processes. This junction includes molecules that are unique to the podocyte that probably determine the correct morphology of the cell, and are targets of disease processes that disrupt the intricate balance of signaling that controls the cytoskeletal matrix. This Review will outline the most recent concepts and advances in our understanding of this critical aspect of glomerular biology, as well as discussing how an improved understanding of the podocyte cytoskeleton is starting to shape advances in delineating the pathogenesis of common glomerular diseases.

Key Points

  • The functional properties of the podocyte cell layer enable control of glomerular filtration

  • The podocyte is highly differentiated and has a unique cytoskeletal architecture, which is dynamically regulated with constant changes in contractility and motility

  • This dynamic regulation is modulated by specialized proteins located at the slit diaphragm complex, which links to the actin cytoskeleton

  • In glomerular disease, the slit diaphragm and cytoskeleton are targeted and disrupted

  • Changes in podocyte motility might underlie the phenotypic changes seen in glomerular disease

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Figure 1: A scanning electron microgram of podocyte cells in a glomerulus demonstrates the cell body, major processes, secondary processes and the finely interdigitating foot processes.
Figure 2: A hypothesis for a spectrum of podocyte migratory changes in nephrotic syndromes.
Figure 3: Reported interactions of slit diaphragm proteins (red) and their downstream effectors with the small GTPases RhoA, Rac1 and Cdc42 (green) via intracellular signaling proteins (orange) leading to regulation of the podocyte cytoskeleton.

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Both authors contributed equally to all aspects of this Review.

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Correspondence to Moin A. Saleem.

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Welsh, G., Saleem, M. The podocyte cytoskeleton—key to a functioning glomerulus in health and disease. Nat Rev Nephrol 8, 14–21 (2012). https://doi.org/10.1038/nrneph.2011.151

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