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Published on: June 15, 2017
Growth factors differentially regulate neuronal Cav channels via ERK-dependent signalling
A J Woodall1, M A Richards, D J Turner
1Faculty of Life Sciences, The University of Manchester, Manchester M13 9NT, UK.
Cell Calcium
|November 13, 2007
Summary
Neurotrophic factors like NGF, GDNF, and EGF regulate voltage-gated calcium channels (Ca(v)) via ERK signaling in sensory neurons. These factors fine-tune calcium influx through distinct mechanisms, impacting neuronal function.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Signaling
Background:
- Voltage-gated calcium channels (Ca(v)) are crucial for neuronal function and are regulated by Ras/extracellular signal-regulated kinase (ERK) signaling.
- The precise mechanisms controlling the specificity of cellular responses to ERK signaling in neurons are not fully understood.
- Neurotrophic factors are known regulators of ERK signaling and play vital roles in neuronal survival, development, and plasticity.
Purpose of the Study:
- To investigate the role of endogenous neurotrophic factors (NGF, GDNF, EGF) in the tonic, ERK-dependent regulation of Ca(v) channels in rat dorsal root ganglion neurons.
- To elucidate the distinct mechanisms and time-frames through which these growth factors modulate Ca(v) channel activity.
- To determine if NGF, GDNF, and EGF differentially regulate specific Ca(v) channel populations.
Main Methods:
- Utilized rat dorsal root ganglion neurons.
- Employed chronic deprivation of growth factors to assess effects on Ca(v) currents.
- Investigated both transcriptional and acute modulatory effects of growth factors on Ca(v) channels.
- Analyzed changes in Ca(v) channel gating and surface expression.
Main Results:
- Endogenous NGF, GDNF, and EGF contribute to tonic ERK-dependent up-regulation of Ca(v) channels.
- Growth factor deprivation altered Ca(v) currents, correlating with changes in receptor expression.
- EGF specifically regulated Ca(v) transcriptional expression, while NGF and GDNF induced rapid, acute modulation of Ca(v) channels (within ~10 min) likely via altered gating.
- NGF, GDNF, and EGF demonstrated differential regulation of specific Ca(v) channel populations.
Conclusions:
- Neurotrophic factors NGF, GDNF, and EGF are key players in the ERK-dependent regulation of Ca(v) channels in sensory neurons.
- These factors offer a flexible system for tailoring calcium influx through both transcriptional and rapid post-translational mechanisms.
- The differential regulation of Ca(v) channels by these factors allows for precise control of neuronal excitability and function.
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