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Expression of temperature-sensitive ion channel TRPM8 in sperm cells correlates with vertebrate evolution.

ABSTRACT: Transient Receptor Potential cation channel, subfamily Melastatin, member 8 (TRPM8) is involved in detection of cold temperature, different noxious compounds and in execution of thermo- as well as chemo-sensitive responses at cellular levels. Here we explored the molecular evolution of TRPM8 by analyzing sequences from various species. We elucidate that several regions of TRPM8 had different levels of selection pressure but the 4th-5th transmembrane regions remain highly conserved. Analysis of synteny suggests that since vertebrate origin, TRPM8 gene is linked with SPP2, a bone morphogen. TRPM8, especially the N-terminal region of it, seems to be highly variable in human population. We found 16,656 TRPM8 variants in 1092 human genomes with top variations being SNPs, insertions and deletions. A total of 692 missense mutations are also mapped to human TRPM8 protein of which 509 seem to be delateroiours in nature as supported by Polyphen V2, SIFT and Grantham deviation score. Using a highly specific antibody, we demonstrate that TRPM8 is expressed endogenously in the testis of rat and sperm cells of different vertebrates ranging from fish to higher mammals. We hypothesize that TRPM8 had emerged during vertebrate evolution (ca 450 MYA). We propose that expression of TRPM8 in sperm cell and its role in regulating sperm function are important factors that have guided its molecular evolution, and that these understandings may have medical importance.

SUBMITTER: Majhi RK

PROVIDER: S-EPMC4614861 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Expression of temperature-sensitive ion channel TRPM8 in sperm cells correlates with vertebrate evolution.

Majhi Rakesh Kumar RK Saha Somdatta S Kumar Ashutosh A Ghosh Arijit A Ghosh Arijit A Swain Nirlipta N Goswami Luna L Mohapatra Pratyush P Maity Apratim A Kumar Sahoo Vivek V Kumar Abhishek A Goswami Chandan C

PeerJ 20151013

Transient Receptor Potential cation channel, subfamily Melastatin, member 8 (TRPM8) is involved in detection of cold temperature, different noxious compounds and in execution of thermo- as well as chemo-sensitive responses at cellular levels. Here we explored the molecular evolution of TRPM8 by analyzing sequences from various species. We elucidate that several regions of TRPM8 had different levels of selection pressure but the 4th-5th transmembrane regions remain highly conserved. Analysis of s ...[more]

PMID: 26500819

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Project description:Highlights • Tunica dartos smooth muscle (TDSM), which is responsible for scrotal thermoregulation, responds to cooling by enhancement of basal tension, and increase of the amplitude and duration of synaptically-evoked contractions.• TDSM cold-induced tension, but not synaptically-evoked contractions are sensitive to the blockers of TRPM8 cold/menthol receptor.• TRPM8 is localized to the TDSM cells' endoplasmic reticulum and its activation by cold causes intracellular calcium mobilization.• Chemical castration of male rats consequent to pharmacological blockade of androgen receptors eliminates the effects of cold on TDSM tension, but not on synaptically-evoked contractions, and abolishes TRPM8 protein expression.• TRPM8 is an important determinant of cold-dependent contractility of the tunica dartos muscle and scrotal thermoregulation which is crucial for maintaining normal spermatogenesis and male fertility. Tunica dartos smooth muscle (TDSM) lies beneath the scrotal skin, and its contraction leads to scrotum wrinkling upon cooling. However, neither the nature of TDSM cold-sensitivity nor the underlying molecular sensors are well understood. Here we have investigated the role of cold/menthol-sensitive TRPM8 channel in TDSM temperature-dependent contractility. The contraction of isolated male rat TDSM strips was studied by tensiometry. TRPM8 expression was assayed by RT-PCR and fluorescence immunochemistry. Isolated TDSM strips responded to cooling from 33 °C to 20 °C by enhancement of basal tension, and increase of the amplitude and duration of electric field stimulated (EFS) contractions. The effects of cold on basal tension, but not on EFS-contractions, could be 80% inhibited by TRPM8 blockers, capsazepine and BCTC [N-(4‑tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide], and could be partially mimicked by menthol. RT-PCR and immunolabeling showed TRPM8 mRNA and protein expression in TDSM cells with protein labelling being predominantly localized to intracellular compartments. Chemical castration of male rats consequent to the treatment with androgen receptor blocker, flutamide, led to the abrogation of cold effects on TDSM basal tension, but not on EFS-contractions, and to the disappearance of TRPM8 protein expression. We conclude that TRPM8 is involved in the maintenance of basal cold-induced TDSM tonus, but not in sympathetic nerve-mediated contractility, by acting as endoplasmic reticulum Ca2+ release channel whose expression in TDSM cells requires the presence of a functional androgen receptor. Thus, TRPM8 plays a crucial role in scrotal thermoregulation which is important for maintaining normal spermatogenesis and male fertility.

Dataset Information

Expression of temperature-sensitive ion channel TRPM8 in sperm cells correlates with vertebrate evolution.

Publications

Expression of temperature-sensitive ion channel TRPM8 in sperm cells correlates with vertebrate evolution.

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