Neurotrophin B receptor kinase increases Kv subfamily member 1.3 (Kv1.3) ion channel half-life and surface expression

B. S. Colley, K. C. Biju, A. Visegrady, S. Campbell, D. A. Fadool

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Kv subfamily member 1.3 (Kv1.3), a member of the Shaker family of potassium channels, has been found to play diverse roles in immunity, metabolism, insulin resistance, sensory discrimination, and axonal targeting in addition to its traditional role in the stabilization of the resting potential. We demonstrate that the neurotrophin B receptor (TrkB) causes an upregulation of Kv1.3 ion channel protein expression in the absence of the preferred ligand for the receptor (brain-derived neurotrophic factor; BDNF) and oppositely downregulates levels of Kv subfamily member 1.5. Although the effect occurs in the absence of the ligand, Kv1.3 upregulation by TrkB is dependent upon the catalytic domain of the TrkB kinase as well as tyrosine (Y) residues in the N and C terminus of the Kv1.3 channel. Using pulse-chase experiments we find that TrkB alters the half-life residence of the channel by approximately 2× and allows it to sustain activity as reflected in an increased current magnitude without alteration of kinetic properties. TrkB and Kv1.3 co-immunoprecipitate from tissue preparations of the mouse olfactory bulb and olfactory cortex, and by immunocytochemical approaches, are found to be co-localized in the glomerular, mitral cell, and internal plexiform layers of the olfactory bulb. These data suggest that Kv1.3 is not only modulated by direct phosphorylation in the presence of BDNF-activated TrkB kinase, but also may be fine tuned via regulation of surface expression while in the proximity of neurotrophic factor receptors. Given the variability of TrkB expression during development, regeneration, or neuronal activation, modulation of surface expression and turnover of Kv channels could significantly impact neuronal excitability, distinct from that of tyrosine kinase phosphorylation.

Original languageEnglish (US)
Pages (from-to)531-546
Number of pages16
JournalNeuroscience
Volume144
Issue number2
DOIs
StatePublished - Jan 19 2007
Externally publishedYes

Keywords

  • Shaker
  • neurotrophins
  • olfactory bulb
  • potassium channel
  • trafficking
  • tyrosine kinase

ASJC Scopus subject areas

  • Neuroscience(all)

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