Pore region of TRPV3 ion channel is specifically required for heat activation.
Ion channels can be activated (gated) by a variety of stimuli, including chemicals, voltage, mechanical force or temperature. Although molecular mechanisms of ion channel gating by chemical and voltage stimuli are understood in principal, the mechanisms of temperature activation remain unknown. The transient receptor potential channel TRPV3 is a nonselective cation channel that is activated by warm temperatures and sensory chemicals such as camphor. Here we screened approcimately 14,000 random mutant clones of mouse TRPV3 and identified five single point mutations that specifically abolish heat activation but do not perturb chemical activation or voltage modulation. Notably, all five mutations are located in the putative sixth transmembrane helix and the adjacent extracellular loop in the pore region of mouse TRPV3. Although distinct in sequence, we found that the corresponding loop of frog TRPV3 is also specifically required for heat activation. These findings demonstrate that the temperature sensitivity of TRPV3 is separable from all other known activation mechanisms and implicate a specific region in temperature sensing.
Grandl
Jörg
J
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Hu
Hongzhen
H
Bandell
Michael
M
Bursulaya
Badry
B
Schmidt
Manuela
M
Petrus
Matt
M
Patapoutian
Ardem
A
D000818:Animals; D001703:Biophysics; D001896:Boron Compounds / Q000494:pharmacology; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D004558:Electric Stimulation; D006358:Hot Temperature; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008958:Models, Molecular; D009154:Mutation / Q000502:physiology; D018408:Patch-Clamp Techniques; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014162:Transfection / Q000379:methods; D014981:Xenopus / Q000235:genetics
D001896:Boron Compounds; D050916:TRPV Cation Channels; C459445:TRPV3 protein, human; C109986:2-aminoethoxydiphenyl borate