TMC-1 Mediates Alkaline Sensation in C. elegans through Nociceptive Neurons.
Noxious pH triggers pungent taste and nocifensive behavior. While the mechanisms underlying acidic pH sensation have been extensively characterized, little is known about how animals sense alkaline pH in the environment. TMC genes encode a family of evolutionarily conserved membrane proteins whose functions are largely unknown. Here, we characterize C. elegans TMC-1, which was suggested to form a Na(+)-sensitive channel mediating salt chemosensation. Interestingly, we find that TMC-1 is required for worms to avoid noxious alkaline environment. Alkaline pH evokes an inward current in nociceptive neurons, which is primarily mediated by TMC-1 and to a lesser extent by the TRP channel OSM-9. However, unlike OSM-9, which is sensitive to both acidic and alkaline pH, TMC-1 is only required for alkali-activated current, revealing a specificity for alkaline sensation. Ectopic expression of TMC-1 confers alkaline sensitivity to alkali-insensitive cells. Our results identify an unexpected role for TMCs in alkaline sensation and nociception.
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Xiang
X
Wang
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
Guang
G
Li
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Jie
J
Liu
College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China; Key Laboratory of Molecular Biophysics of MOE, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
Jianfeng
J
Liu
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: shawnxu@umich.edu.
X Z Shawn
XZ
Xu
D000818:Animals; D017173:Caenorhabditis elegans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism*; D012677:Sensation / Q000502:physiology; D029742:Caenorhabditis elegans Proteins
D007473:Ion Channels; D009419:Nerve Tissue Proteins; C578678:TMC-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins