TRPV1 recapitulates native capsaicin receptor in sensory neurons in association with Fas-associated factor 1.
TRPV1, a cloned capsaicin receptor, is a molecular sensor for detecting adverse stimuli and a key element for inflammatory nociception and represents biophysical properties of native channel. However, there seems to be a marked difference between TRPV1 and native capsaicin receptors in the pharmacological response profiles to vanilloids or acid. One plausible explanation for this overt discrepancy is the presence of regulatory proteins associated with TRPV1. Here, we identify Fas-associated factor 1 (FAF1) as a regulatory factor, which is coexpressed with and binds to TRPV1 in sensory neurons. When expressed heterologously, FAF1 reduces the responses of TRPV1 to capsaicin, acid, and heat, to the pharmacological level of native capsaicin receptor in sensory neurons. Furthermore, silencing FAF1 by RNA interference augments capsaicin-sensitive current in native sensory neurons. We therefore conclude that FAF1 forms an integral component of the vanilloid receptor complex and that it constitutively modulates the sensitivity of TRPV1 to various noxious stimuli in sensory neurons.
Kim
Sangsung
S
Sensory Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Kang
Changjoong
C
Shin
Chan Young
CY
Hwang
Sun Wook
SW
Yang
Young Duk
YD
Shim
Won Sik
WS
Park
Min-Young
MY
Kim
Eunhee
E
Kim
Misook
M
Kim
Byung-Moon
BM
Cho
Hawon
H
Shin
Youngki
Y
Oh
Uhtaek
U
D000143:Acids / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D051017:Apoptosis Regulatory Proteins; D019921:Biotinylation / Q000379:methods; D015153:Blotting, Western / Q000379:methods / Q000706:statistics & numerical data; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D003001:Cloning, Molecular / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D009154:Mutation; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D017434:Protein Structure, Tertiary / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050916:TRPV Cation Channels / Q000502:physiology*; D013696:Temperature; D014162:Transfection / Q000379:methods; D025801:Ubiquitin / Q000378:metabolism
D000143:Acids; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C490780:FAF1 protein, human; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D025801:Ubiquitin; D002211:Capsaicin