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PMID: 17959807 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

A role of the transient receptor potential domain of vanilloid receptor I in channel gating.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 27 ·No. 43 ·2007-10-24 ·Pages 11641-50

García-Sanz N, Valente P, Gomis A, Fernández-Carvajal A, Fernández-Ballester G, Viana F, Belmonte C, Ferrer-Montiel A

Abstract

Transient receptor potential vanilloid receptor subtype 1 (TRPV1) is an ionotropic receptor activated by temperature and chemical stimuli. The C-terminal region that is adjacent to the channel gate, recognized as the TRP domain, is a molecular determinant of receptor assembly. However, the role of this intracellular domain in channel function remains elusive. Here, we show that replacement of the TRP domain of TRPV1 with the cognate region of TRPV channels (TRPV2-TRPV6) did not affect receptor assembly and trafficking to the cell surface, although those receptors containing the TRP domain of the distantly related TRPV5 and TRPV6 did not display ion channel activity. Notably, functional chimeras exhibited an impaired sensitivity to the activating stimuli, consistent with a significant contribution of this protein domain to channel function. At variance with TRPV1, voltage-dependent gating of chimeric channels could not be detected in the absence of capsaicin and/or heat. Biophysical analysis of functional chimeras revealed that the TRP domain appears to act as a molecular determinant of the activation energy of channel gating. Together, these findings uncover a role of the TRP domain in intersubunit interactions near the channel gate that contribute to the coupling of stimulus sensing to channel opening.

MeSH Terms
Amino Acid Sequence Amino Acid Substitution/genetics Animals Cell Line Female Humans Ion Channel Gating/genetics,physiology Mice Molecular Sequence Data Peptide Fragments/genetics,physiology Protein Subunits/genetics,metabolism,physiology Protein Transport/genetics,physiology TRPV Cation Channels/genetics,metabolism,physiology Xenopus
Chemicals
Peptide Fragments Protein Subunits TRPV Cation Channels TRPV1 protein, mouse
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
García-Sanz Nuria
Instituto de Biología Molecular y Celular, Consejo Superior de Investigaciones Científicas, Universidad Miguel Hernández, 03202 Elche, Alicante, Spain.
Valente Pierluigi
Gomis Ana
Fernández-Carvajal Asia
Fernández-Ballester Gregorio
Viana Felix
Belmonte Carlos
Ferrer-Montiel Antonio
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.2457-07.2007
Published
2007-10-24
Pages
11641-50
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6673226
Subset
IM
External Links
PubMed source DOI: 10.1523/JNEUROSCI.2457-07.2007 PMC Full Text View journal details
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