A novel domain regulating degradation of the glomerular slit diaphragm protein podocin in cell culture systems

PLoS One. 2013;8(2):e57078. doi: 10.1371/journal.pone.0057078. Epub 2013 Feb 20.

Abstract

Mutations in the gene NPHS2 are the most common cause of hereditary steroid-resistant nephrotic syndrome. Its gene product, the stomatin family member protein podocin represents a core component of the slit diaphragm, a unique structure that bridges the space between adjacent podocyte foot processes in the kidney glomerulus. Dislocation and misexpression of slit diaphragm components have been described in the pathogenesis of acquired and hereditary nephrotic syndrome. However, little is known about mechanisms regulating cellular trafficking and turnover of podocin. Here, we discover a three amino acids-comprising motif regulating intracellular localization of podocin in cell culture systems. Mutations of this motif led to markedly reduced degradation of podocin. These findings give novel insight into the molecular biology of the slit diaphragm protein podocin, enabling future research to establish the biological relevance of podocin turnover and localization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Line
  • Cell Membrane / metabolism
  • Endosomes / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Membrane Microdomains
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mutation
  • Protein Interaction Domains and Motifs*
  • Protein Transport
  • Proteolysis

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein

Grant support

This study was supported by Else Kröner-Fresenius-Stiftung (http://www.ekfs.de/, TBH), Deutsche Forschungsgemeinschaft (http://www.dfg.de/, TBH), the Excellence Initiative of the German Federal and State Governments EXC 294 (http://www.bioss.uni-freiburg.de/, TBH) and Deutsche Gesellschaft für Nephrologie (http://dgfn.eu/, MG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.