TRPV3 is a temperature-sensitive vanilloid receptor-like protein.
Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic pH and the alkaloid irritant capsaicin. Although VR1 gene disruption results in a loss of capsaicin responses, it has minimal effects on thermal nociception. This and other experiments--such as those showing the existence of capsaicin-insensitive heat sensors in sensory neurons--suggest the existence of thermosensitive receptors distinct from VR1. Here we identify a member of the vanilloid receptor/TRP gene family, vanilloid receptor-like protein 3 (VRL3, also known as TRPV3), which is heat-sensitive but capsaicin-insensitive. VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1. VRL3 responds to noxious heat with a threshold of about 39 degrees C and is co-expressed in dorsal root ganglion neurons with VR1. Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses. Hence, not only is VRL3 a thermosensitive ion channel but it may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels.
Smith
G D
GD
Neurology-CEDD, GlaxoSmithKline, Third Avenue, Harlow CM19 5AW, UK.
Gunthorpe
M J
MJ
Kelsell
R E
RE
Hayes
P D
PD
Reilly
P
P
Facer
P
P
Wright
J E
JE
Jerman
J C
JC
Walhin
J-P
JP
Ooi
L
L
Egerton
J
J
Charles
K J
KJ
Smart
D
D
Randall
A D
AD
Anand
P
P
Davis
J B
JB
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D027682:Cation Transport Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D006358:Hot Temperature; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011485:Protein Binding; D021122:Protein Subunits; D011522:Protons; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011955:Receptors, Drug / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017385:Sequence Homology; D050916:TRPV Cation Channels
D027682:Cation Transport Proteins; D007473:Ion Channels; D021122:Protein Subunits; D011522:Protons; D012333:RNA, Messenger; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C459445:TRPV3 protein, human; D002211:Capsaicin; D002118:Calcium