UNC80 functions as a scaffold for Src kinases in NALCN channel function

Channels (Austin). 2009 May-Jun;3(3):161-3. doi: 10.4161/chan.3.3.8853. Epub 2009 May 27.

Abstract

Ion channels can be regulated by a wide spectrum of neurotransmitters and hormones, largely through G-protein-coupled receptors (GPCRs). G-protein-independent activation of ion channel currents by GPCRs has also been recorded, although the molecular identity of the channels and the activation mechanisms remain largely unknown. UNC80 is a protein that is associated with the NALCN Na(+) leak cation channel, and is required for the activation of this channel by the neuropeptide substance P through GPCRs in a G-protein-independent fashion. Here, we show that UNC80 binds Src kinases and recruits Src into the channel complex. This finding is consistent with the known requirement for Src kinases in the activation of NALCN, and may lead to new insights into the molecular mechanisms underlying G-protein-independent activation of the channel.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Humans
  • Ion Channels
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding / physiology
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*

Substances

  • Carrier Proteins
  • Ion Channels
  • Membrane Proteins
  • NALCN protein, human
  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled
  • Sodium Channels
  • Unc80 protein, human
  • src-Family Kinases