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The p38 mitogen-activated protein kinase pathway negatively regulates Ca2+-activated K+ channel trafficking in

Kwon-Seok Chae1, Stuart E Dryer

  • 1Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5513, USA.

Journal of Neurochemistry
|July 7, 2005
PubMed

Insights

The p38 signaling pathway inhibits large-conductance Ca2+-activated K+ channels (K(Ca)) trafficking in neurons. This pathway stabilizes actin, preventing channel insertion into the plasma membrane.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Large-conductance Ca2+-activated K+ channels (K(Ca)) trafficking in neurons is crucial for neuronal function.
  • Growth factors regulate K(Ca) channel trafficking, but the underlying molecular mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the role of the p38 signaling cascade in regulating K(Ca) channel trafficking in chick ciliary ganglion neurons.
  • To elucidate the molecular mechanisms by which p38 signaling influences K(Ca) channel surface expression.

Main Methods:

  • Utilized p38 inhibitors (SB202190, SB203580) and dominant-negative constructs to modulate p38 activity.
  • Assessed K(Ca) channel expression using immunochemical methods.
  • Investigated the role of filamentous actin (F-actin) dynamics in K(Ca) trafficking.
  • Examined the effects of transforming growth factor (TGF) beta3 on p38 phosphorylation and F-actin.

Main Results:

  • Inhibition of p38 signaling increased K(Ca) channel expression in ciliary neurons.
  • p38 signaling acts at a distal step in the trafficking pathway, independent of protein synthesis or Golgi processing.
  • Depolymerization of F-actin enhanced K(Ca) functional expression, while F-actin stabilization inhibited the p38 inhibitor's effect.
  • p38 inhibition reduced cortical F-actin, and TGFbeta3 increased p38 phosphorylation and cortical F-actin.

Conclusions:

  • The p38 signaling cascade endogenously suppresses functional K(Ca) channel expression by stabilizing F-actin, which acts as a barrier to plasma membrane insertion.
  • This p38 cascade mediates the inhibitory effects of TGFbeta3 on K(Ca) channel expression in ciliary neurons.

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