How are ion pumps and agrin signaling integrated?

Trends Biochem Sci. 2010 Dec;35(12):653-9. doi: 10.1016/j.tibs.2010.05.004. Epub 2010 Jun 11.


Na(+),K(+)-ATPase (NKA) has a fundamental role in ion transport across the plasma membrane of animal cells and uses approximately 50% of brain energy consumption. Recent work has uncovered additional roles for NKA in signal transduction. How might such different functions of the sodium-potassium pump be connected and regulated? We envision an integrated model of ion pumping and signaling, considering in particular the recently discovered regulation of the sodium-potassium pump by agrin, a protein that is cleaved specifically by neurotrypsin at the synapse. Based on the recently solved structure of NKA and sequence analysis, we propose a molecular model for the agrin-NKA interaction, in which agrin displaces the NKA β-subunit and exploits the ouabain-binding pocket.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agrin / chemistry
  • Agrin / metabolism*
  • Animals
  • Models, Molecular
  • Signal Transduction*
  • Sodium-Potassium-Exchanging ATPase / chemistry
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Agrin
  • Sodium-Potassium-Exchanging ATPase