Nociceptive signals induce trafficking of TRPA1 to the plasma membrane.
Transient receptor potential A1 (TRPA1) ion channel senses a variety of noxious stimuli and is involved in nociception. Many TRPA1 agonists covalently modify the channel, which can lead to desensitization. The fate of modified TRPA1 and the mechanism of preserving its response to subsequent stimuli are not understood. Moreover, inflammatory signals sensitize TRPA1 by involving protein kinase A (PKA) and phospholipase C (PLC) through unknown means. We show that TRPA1-mediated nocifensive behavior can be sensitized in vivo via PKA/PLC signaling and by activating TRPA1 with the ligand mustard oil (MO). Interestingly, both stimuli increased TRPA1 membrane levels in vitro. Tetanus toxin attenuated the response to the second of two pulses of MO in neurons, suggesting that vesicle fusion increases functional surface TRPA1. Capacitance recordings suggest that MO can induce exocytosis. We propose that TRPA1 translocation to the membrane might represent one of the mechanisms controlling TRPA1 functionality upon acute activation or inflammatory signals.
Schmidt
Manuela
M
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Dubin
Adrienne E
AE
Petrus
Matt J
MJ
Earley
Taryn J
TJ
Patapoutian
Ardem
A
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology
D018836:Inflammation Mediators; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D010738:Type C Phospholipases