Dataset Information

Conserved residues within the putative S4-S5 region serve distinct functions among thermosensitive vanilloid transient receptor potential (TRPV) channels.

ABSTRACT: The vanilloid transient receptor potential channel TRPV1 is a tetrameric six-transmembrane segment (S1-S6) channel that can be synergistically activated by various proalgesic agents such as capsaicin, protons, heat, or highly depolarizing voltages, and also by 2-aminoethoxydiphenyl borate (2-APB), a common activator of the related thermally gated vanilloid TRP channels TRPV1, TRPV2, and TRPV3. In these channels, the conserved charged residues in the intracellular S4-S5 region have been proposed to constitute part of a voltage sensor that acts in concert with other stimuli to regulate channel activation. The molecular basis of this gating event is poorly understood. We mutated charged residues all along the S4 and the S4-S5 linker of TRPV1 and identified four potential voltage-sensing residues (Arg(557), Glu(570), Asp(576), and Arg(579)) that, when specifically mutated, altered the functionality of the channel with respect to voltage, capsaicin, heat, 2-APB, and/or their interactions in different ways. The nonfunctional charge-reversing mutations R557E and R579E were partially rescued by the charge-swapping mutations R557E/E570R and D576R/R579E, indicating that electrostatic interactions contribute to allosteric coupling between the voltage-, temperature- and capsaicin-dependent activation mechanisms. The mutant K571E was normal in all aspects of TRPV1 activation except for 2-APB, revealing the specific role of Lys(571) in chemical sensitivity. Surprisingly, substitutions at homologous residues in TRPV2 or TRPV3 had no effect on temperature- and 2-APB-induced activity. Thus, the charged residues in S4 and the S4-S5 linker contribute to voltage sensing in TRPV1 and, despite their highly conserved nature, regulate the temperature and chemical gating in the various TRPV channels in different ways.

SUBMITTER: Boukalova S

PROVIDER: S-EPMC3009871 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Conserved residues within the putative S4-S5 region serve distinct functions among thermosensitive vanilloid transient receptor potential (TRPV) channels.

Boukalova Stepana S Marsakova Lenka L Teisinger Jan J Vlachova Viktorie V

The Journal of biological chemistry 20101102 53

The vanilloid transient receptor potential channel TRPV1 is a tetrameric six-transmembrane segment (S1-S6) channel that can be synergistically activated by various proalgesic agents such as capsaicin, protons, heat, or highly depolarizing voltages, and also by 2-aminoethoxydiphenyl borate (2-APB), a common activator of the related thermally gated vanilloid TRP channels TRPV1, TRPV2, and TRPV3. In these channels, the conserved charged residues in the intracellular S4-S5 region have been proposed ...[more]

PMID: 21044960

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Project description:The transient receptor potential vanilloid (TRPV) ion channel family is involved in multiple sensory and physiological functions including thermosensing and temperature-dependent neuroendocrine regulation. The objective of the present study was to investigate the number, origin and evolution of TRPV genes in metazoans, with special focus on the impact of the vertebrate whole-genome duplications (WGD). Gene searches followed by phylogenetic and synteny analyses revealed multiple previously undescribed TRPV genes. The common ancestor of Cnidaria and Bilateria had three TRPV genes that became four in the deuterostome ancestor. Two of these were lost in the vertebrate ancestor. The remaining two genes gave rise to two TRPV subfamilies in vertebrates, consisting of subtypes 1, 2, 3, 4, 9 and 5, 6, 7, 8, respectively. This gene expansion resulted from the two basal vertebrate WGD events (1R and 2R) and three local duplications before the radiation of gnathostomes. TRPV1, 4 and 5 have been retained in all gnathostomes investigated, presumably reflecting important functions. TRPV7 and 8 have been lost independently in various lineages but are still retained in cyclostomes, actinistians (coelacanth), amphibians, prototherians and basal actinopterygians (Polypteridae). TRPV3 and 9 are present in extant elasmobranchs, while TRPV9 was lost in the osteichthyan ancestor and TRPV3 in the actinopterygian ancestor. The coelacanth has retained the ancestral osteichthyan repertoire of TRPV1, 3, 4, 5, 7 and 8. TRPV2 arose in the tetrapod ancestor. Duplications of TRPV5 occurred independently in various lineages, such as cyclostomes, chondrichthyans, anuran amphibians, sauropsids, mammals (where the duplicate is called TRPV6), and actinopterygians (Polypteridae and Esocidae). After the teleost-specific WGD (3R) only TRPV1 retained its duplicate, whereas TRPV4 and 5 remained as single genes. Both 3R-paralogs of TRPV1 were kept in some teleost species, while one paralog was lost in others. The salmonid-specific WGD (4R) duplicated TRPV1, 4, and 5 leading to six TRPV genes. The largest number was found in Xenopus tropicalis with no less than 15 TRPV genes. This study provides a comprehensive evolutionary scenario for the vertebrate TRPV family, revealing additional TRPV types and proposing a phylogeny-based classification of TRPV across metazoans.

Dataset Information

Conserved residues within the putative S4-S5 region serve distinct functions among thermosensitive vanilloid transient receptor potential (TRPV) channels.

Publications

Conserved residues within the putative S4-S5 region serve distinct functions among thermosensitive vanilloid transient receptor potential (TRPV) channels.

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