Nerve injury induces a Gem-GTPase-dependent downregulation of P/Q-type Ca2+ channels contributing to neurite plasticity in dorsal root ganglion neurons

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• 作者：Frédérique Scamps ; Sina Sangari…
• 关键词：Sensory neuron ; High ; voltage ; activated Ca2+ current ; RGK ; Proprioceptor ; Mechanoreceptor
• 刊名：Pflügers Archiv - European Journal of Physiology
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：467
• 期：2
• 页码：351-366
• 全文大小：2,110 KB
• 参考文献：1. Andre S, Puech-Mallie S, Desmadryl G, Valmier J, Scamps F (2003) Axotomy differentially regulates voltage-gated calcium currents in mice sensory neurones. Neuroreport 14(1):147-50 CrossRef
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  11. Charnet P, Scamps F, Rousset M, Menard C, Bellis M, Cens T (2013) RGK small GTPases and Regulation of Cav2 channels. In: Stephens G, Mochida S (eds) Modulation of presynaptic calcium channels. Springer, Dordrecht
  12. Chen H, Puhl HL 3rd, Niu SL, Mitchell DC, Ikeda SR (2005) Expression of Rem2, an RGK family small GTPase, reduces N-type calcium current without affecting channel surface density. J Neurosci 25(42):9762-772 CrossRef
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• 作者单位：Frédérique Scamps (1) (3)
  Sina Sangari (1)
  Melissa Bowerman (1) (3)
  Mathieu Rousset (2) (3)
  Michel Bellis (2) (3)
  Thierry Cens (2) (3)
  Pierre Charnet (2) (3)
  
  1. Inserm U1051, Institut des Neurosciences, 80 rue Augustin Fliche, 34091, Montpellier, France
  3. Universités de Montpellier I&II, 34293, Montpellier, France
  2. CRBM, CNRS UMR5237, 1919 Route de Mende, 34293, Montpellier, France
  
• 刊物主题：Human Physiology;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-2013

文摘

Small RGK GTPases, Rad, Gem, Rem1, and Rem2, are potent inhibitors of high-voltage-activated (HVA) Ca2+ channels expressed in heterologous expression systems. However, the role of this regulation has never been clearly demonstrated in the nervous system. Using transcriptional analysis, we show that peripheral nerve injury specifically upregulates Gem in mice dorsal root ganglia. Following nerve injury, protein expression was increased in ganglia and peripheral nerve, mostly under its phosphorylated form. This was confirmed in situ and in vitro in dorsal root ganglia sensory neurons. Knockdown of endogenous Gem, using specific small-interfering RNA (siRNA), increased the HVA Ca2+ current only in the large-somatic-sized neurons. Combining pharmacological analysis of the HVA Ca2+ currents together with Gem siRNA-transfection of larger sensory neurons, we demonstrate that only the P/Q-type Ca2+ channels were enhanced. In vitro analysis of Gem affinity to various CaVβx-CaV2.x complexes and immunocytochemical studies of Gem and CaVβ expression in sensory neurons suggest that the specific inhibition of the P/Q channels relies on both the regionalized upregulation of Gem and the higher sensitivity of the endogenous CaV2.1-CaVβ4 pair in a subset of sensory neurons including the proprioceptors. Finally, pharmacological inhibition of P/Q-type Ca2+ current reduces neurite branching of regenerating axotomized neurons. Taken together, the present results indicate that a Gem-dependent P/Q-type Ca2+ current inhibition may contribute to general homeostatic mechanisms following a peripheral nerve injury.