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Estrogen destabilizes microtubules through an ion‐conductivity‐independent TRPV1 pathway
Author(s) -
Goswami Chandan,
Kuhn Julia,
Dina Olayinka A.,
FernándezBallester Gregorio,
Levine Jon D.,
FerrerMontiel Antonio,
Hucho Tim
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07270.x
Subject(s) - trpv1 , gper , phosphorylation , chemistry , microtubule , protein kinase c , microbiology and biotechnology , microtubule polymerization , estrogen receptor , transient receptor potential channel , biophysics , tubulin , biology , biochemistry , receptor , medicine , cancer , breast cancer
J. Neurochem. (2011) 117 , 995–1008. Abstract 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.