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Cytoplasmic Inter-Subunit Interface Controls Use-Dependence of Thermal Activation of TRPV3 Channel
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SYSNO ASEP 0510414 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Cytoplasmic Inter-Subunit Interface Controls Use-Dependence of Thermal Activation of TRPV3 Channel Author(s) Máčiková, Lucie (FGU-C) ORCID, RID
Vyklická, Lenka (FGU-C) ORCID, RID, SAI
Barvík, I. (CZ)
Sobolevsky, A. I. (US)
Vlachová, Viktorie (FGU-C) RID, ORCID, SAIArticle number 3990 Source Title International Journal of Molecular Sciences. - : MDPI
Roč. 20, č. 16 (2019)Number of pages 18 s. Language eng - English Country CH - Switzerland Keywords transient receptor potential ; transient receptor potential vanilloid 1 (TRPV1) ; noxious heat ; ankyrin repeat ; nociception Subject RIV FH - Neurology OECD category Neurosciences (including psychophysiology R&D Projects GA19-03777S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000484411100147 EID SCOPUS 85071477682 DOI 10.3390/ijms20163990 Annotation The vanilloid transient receptor potential channel TRPV3 is a putative molecular thermosensor widely considered to be involved in cutaneous sensation, skin homeostasis, nociception, and pruritus. Repeated stimulation of TRPV3 by high temperatures above 50 degrees C progressively increases its responses and shifts the activation threshold to physiological temperatures. This use-dependence does not occur in the related heat-sensitive TRPV1 channel in which responses decrease, and the activation threshold is retained above 40 degrees C during activations. By combining structure-based mutagenesis, electrophysiology, and molecular modeling, we showed that chimeric replacement of the residues from the TRPV3 cytoplasmic inter-subunit interface (N251-E257) with the homologous residues of TRPV1 resulted in channels that, similarly to TRPV1, exhibited a lowered thermal threshold, were sensitized, and failed to close completely after intense stimulation. Crosslinking of this interface by the engineered disulfide bridge between substituted cysteines F259C and V385C (or, to a lesser extent, Y382C) locked the channel in an open state. On the other hand, mutation of a single residue within this region (E736) resulted in heat resistant channels. We propose that alterations in the cytoplasmic inter-subunit interface produce shifts in the channel gating equilibrium and that this domain is critical for the use-dependence of the heat sensitivity of TRPV3. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2020 Electronic address https://doi.org/10.3390/ijms20163990
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