A specialized pore turret in the mammalian cation channel TRPV1 is responsible for distinct and species-specific heat activation thresholds

Guangxu Du, Yuhua Tian, Zhihao Yao, Simon Vu, Jie Zheng, Longhui Chai, Ke Wei Wang, Shilong Yang

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The transient receptor potential vanilloid 1 (TRPV1) channel is a heat-activated cation channel that plays a crucial role in ambient temperature detection and thermal homeostasis. Although several structural features of TRPV1 have been shown to be involved in heat-induced activation of the gating process, the physiological significance of only a few of these key elements has been evaluated in an evolutionary context. Here, using transient expression in HEK293 cells, electrophysiological recordings, and molecular modeling, we show that the pore turret contains both structural and functional determinants that set the heat activation thresholds of distinct TRPV1 orthologs in mammals whose body temperatures fluctuate widely. We found that TRPV1 from the bat Carollia brevicauda exhibits a lower threshold temperature of channel activation than does its human ortholog and three bat-specific amino acid substitutions located in the pore turret are sufficient to determine this threshold temperature. Furthermore, the structure of the TRPV1 pore turret appears to be of physiological and evolutionary significance for differentiating the heat-activated threshold among species-specific TRPV1 orthologs. These findings support a role for the TRPV1 pore turret in tuning the heat-activated threshold, and they suggest that its evolution was driven by adaption to specific physiological traits among mammals exposed to variable temperatures.

Original languageEnglish (US)
Pages (from-to)9641-9649
Number of pages9
JournalThe Journal of biological chemistry
Volume295
Issue number28
DOIs
StatePublished - Jul 10 2020

Keywords

  • bat
  • body temperature regulation
  • cation channel
  • cell biology
  • channel activation
  • electrophysiology
  • heat activation
  • ion channel
  • molecular evolution
  • pore turret
  • thermal homeostasis
  • threshold temperature
  • transient receptor potential channels (TRP channels)
  • transient receptor potential vanilloid 1 (TRPV1)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A specialized pore turret in the mammalian cation channel TRPV1 is responsible for distinct and species-specific heat activation thresholds'. Together they form a unique fingerprint.

  • Cite this