Lipid-protein interactions along the slit diaphragm of podocytes

J Am Soc Nephrol. 2009 Mar;20(3):473-8. doi: 10.1681/ASN.2008070694. Epub 2009 Feb 25.

Abstract

Podocytes are visceral epithelial cells supporting the function of the glomerular filter. Interdigitating foot processes of podocytes enwrap the glomerular capillaries and are connected by a highly specialized cell junction, the slit diaphragm. Signal transduction at the slit diaphragm is essential for the proper function of the kidney filtration barrier. The slit diaphragm constitutes a dynamic multiprotein signaling complex that contains structural proteins, receptors, signaling adaptors, ion channels, and scaffolding proteins. Function of some of these proteins requires cholesterol attached to the multiprotein complex. Recruitment of cholesterol is achieved through the PHB domain protein podocin, a member of a novel family of lipid-binding proteins that are conserved through evolution. The finding that cholesterol interaction regulates the activity of ion channels at the glomerular filtration barrier has important implications for renal physiology and pathophysiology.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cholesterol / metabolism
  • Humans
  • Intercellular Junctions / metabolism
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lipoylation
  • Macromolecular Substances / metabolism
  • Mechanotransduction, Cellular
  • Membrane Lipids / metabolism*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Podocytes / metabolism*
  • Podocytes / ultrastructure
  • Signal Transduction

Substances

  • Caenorhabditis elegans Proteins
  • Intracellular Signaling Peptides and Proteins
  • MEC-2 protein, C elegans
  • Macromolecular Substances
  • Membrane Lipids
  • Membrane Proteins
  • NPHS2 protein
  • Cholesterol