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  • Review Article
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Clinical impact of research on the podocyte slit diaphragm

Nature Clinical Practice Nephrology volume 2, pages 271–282 (2006)Cite this article

Abstract

This Review summarizes recent research on the podocyte slit diaphragm. A growing number of molecules that function at the slit diaphragm have been identified in patients with inherited and sporadic nephrotic syndromes. Genetic deletion of nearly all of these molecules results in proteinuria and effacement of foot processes. Nephrin, Neph1 and podocin seem to form a multifunctional receptor complex at the slit diaphragm. Most of the other components of the slit diaphragm interact directly with this complex, in many cases coupling slit diaphragm components to the podocyte's actin cytoskeleton. These molecular findings are being applied to patients with glomerular disease. Over the next decade, these data might help to improve disease classification and prediction of which patients will respond to immunosuppressive treatment.

Key Points

  • Mutations of molecules that function at the podocyte slit diaphragm of the glomerular filter have recently been identified in patients with inherited and sporadic nephrotic syndromes

  • Experimental deletion of many slit diaphragm molecules induces the proteinuria and effacement of podocyte foot processes that are characteristic of all glomerular diseases

  • Data indicate that three molecules susceptible to mutation—nephrin, Neph1 and podocin—form a receptor complex at the slit diaphragm that interacts with the podocyte actin cytoskeleton

  • Determining the slit diaphragm genetic profile of patients with glomerular diseases should improve disease classification and tailoring of treatment

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Figure 1: The podocyte and slit diaphragm.
Figure 2: Detailed electron tomograph of the slit diaphragm with wire frame representation of electron density.

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Acknowledgements

We thank other researchers for their forbearance, as there were many interesting observations that could not be included herein because of limited space.

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  1. Division of Nephrology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA

    Duncan B Johnstone & Lawrence B Holzman

  2. Associate Professor,

    Duncan B Johnstone & Lawrence B Holzman

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Correspondence to Lawrence B Holzman.

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Johnstone, D., Holzman, L. Clinical impact of research on the podocyte slit diaphragm. Nat Rev Nephrol 2, 271–282 (2006). https://doi.org/10.1038/ncpneph0180

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