Genetic variants affecting human TRPA1 or TRPM8 structure can be classified in vitro as 'well expressed', 'poorly expressed' or 'salvageable'

Bioscience Reports
Kevin MorganAlyn H Morice

Abstract

Multiple mis-sense variants of TRPA1 (transient receptor potential A1) and TRPM8 (transient receptor potential M8) are recorded in the human genome single nt polymorphism (SNP) database, but their potential impact on channel signalling in patho-physiology is not fully explored. Variants, mostly quite rare in the general human population, alter sites in different structural domains of these homo-tetrameric ion channel proteins. The effects of individual SNPs affecting the large cytoplasmic N-terminal domain have not been completely documented for TRPM8 or TRPA1. We examined the Ca(2+) signalling properties of a short-list of eight variants affecting the N-terminal domain by individual expression in human embryonic kidney HEK293 or neuroblastoma (SH-SY5Y) cell lines (four SNP variants for TRPM8: G150R, K423N, R475C, R485W and four for TRPA1: Y69C, A366D, E477K, D573A). These were compared with TRPA1 SNP variants affecting intracellular loops located beyond the N-terminal domain and associated with gain of function (such as increased sensitivity to agonists: TRPA1 R797T and N855S). A substitution in TRPA1 (Y69C) exhibited high expression/sensitivity to agonists (high iCa(2+)max (maximum level of intracellular calcium ion), similar...Continue Reading

References

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Citations

Sep 17, 2016·Headache·Greg Dussor, Yu-Qing Cao
Mar 10, 2017·Molecular Carcinogenesis·Eric VancauwenbergheMorad Roudbaraki
Jul 25, 2019·International Journal of Molecular Sciences·Yasunori TakayamaMakoto Tominaga
Nov 2, 2019·Physiological Reviews·Karel TalaveraBernd Nilius
Mar 9, 2020·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Birol Özkal, İshak Suat Övey
May 24, 2020·Pflügers Archiv : European journal of physiology·Robbe NaertKarel Talavera
Oct 31, 2020·International Journal of Molecular Sciences·Kristyna BarvikovaViktorie Vlachova

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Methods Mentioned

BETA
PCR
transfection

Software Mentioned

Graphpad Prism
NetPhos2
Clustalw2
NetPhos
Scansite

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