Advances in slit diaphragm signaling

Curr Opin Nephrol Hypertens. 2014 Jul;23(4):420-30. doi: 10.1097/01.mnh.0000447018.28852.b6.

Abstract

Purpose of review: The podocyte slit diaphragm is a fundamental component of the glomerular filtration barrier and its function is highly dependent on the maintenance of specialized actin-based projections known as foot processes. In this review, we update the function of key slit diaphragm-associated proteins, and introduce some new players and emerging avenues of research within podocyte biology.

Recent findings: Studies using rodent models continue to support the long-held belief that precise regulation of actin dynamics at the slit diaphragm is essential for proper foot process organization. However, it is also becoming increasingly clear that alterations in actin remodeling can significantly contribute to damage in both animal models and human disease. In particular, the importance of signaling via the Rho family of GTPases has been recognized, as well as the requirement for proper localization and turnover of the slit diaphragm.

Summary: Regulation of the connection between the slit diaphragm and the podocyte actin network requires complex interplay between multiple signaling pathways. New discoveries contribute to an ever-expanding view of the slit diaphragm and serve to create a framework for the development of new therapeutic strategies targeting podocyte function in the future.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Actins / metabolism*
  • Animals
  • Endocytosis
  • Humans
  • Intercellular Junctions / physiology*
  • Kidney Glomerulus / physiology*
  • Membrane Proteins / metabolism*
  • Podocytes / metabolism*
  • Signal Transduction / physiology*
  • cdc42 GTP-Binding Protein / metabolism
  • rac1 GTP-Binding Protein / metabolism
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Actins
  • Membrane Proteins
  • nephrin
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein