These authors contributed equally to this study.
Estrogen destabilizes microtubules through an ion-conductivity-independent TRPV1 pathway
Article first published online: 13 MAY 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 117, Issue 6, pages 995–1008, June 2011
How to Cite
Goswami, C., Kuhn, J., Dina, O. A., Fernández-Ballester, G., Levine, J. D., Ferrer-Montiel, A. and Hucho, T. (2011), Estrogen destabilizes microtubules through an ion-conductivity-independent TRPV1 pathway. Journal of Neurochemistry, 117: 995–1008. doi: 10.1111/j.1471-4159.2011.07270.x
- Issue published online: 1 JUN 2011
- Article first published online: 13 MAY 2011
- Accepted manuscript online: 11 APR 2011 05:42AM EST
- Received April 21, 2010; revised manuscript received December 21, 2010; accepted March 30, 2011.
- conductance independent effects;
J. Neurochem. (2011) 117, 995–1008.
Recently, we described estrogen and agonists of the G-protein coupled estrogen receptor GPR30 to induce protein kinase C (PKC)ε-dependent pain sensitization. PKCε phosphorylates the ion channel transient receptor potential, vanilloid subclass I (TRPV1) close to a novel microtubule-TRPV1 binding site. We now modeled the binding of tubulin to the TRPV1 C-terminus. The model suggests PKCε phosphorylation of TRPV1-S800 to abolish the tubulin-TRPV1 interaction. Indeed, in vitro PKCε phosphorylation of TRPV1 hindered tubulin-binding to TRPV1. In vivo, treatment of sensory neurons and F-11 cells with estrogen and the GPR30 agonist, G-1, resulted in microtubule destabilization and retraction of microtubules from filopodial structures. We found estrogen and G-1 to regulate the stability of the microtubular network via PKC phosphorylation of the PKCε-phosphorylation site TRPV1-S800. Microtubule disassembly was not, however, dependent on TRPV1 ion conductivity. TRPV1 knock-down in rats inverted the effect of the microtubule-modulating drugs, Taxol and Nocodazole, on estrogen-induced and PKCε-dependent mechanical pain sensitization. Thus, we suggest the C-terminus of TRPV1 to be a signaling intermediate downstream of estrogen and PKCε, regulating microtubule-stability and microtubule-dependent pain sensitization.