C. elegans TRP family protein TRP-4 is a pore-forming subunit of a native mechanotransduction channel.
Mechanotransduction channels mediate several common sensory modalities such as hearing, touch, and proprioception; however, very little is known about the molecular identities of these channels. Many TRP family channels have been implicated in mechanosensation, but none have been demonstrated to form a mechanotransduction channel, raising the question of whether TRP proteins simply play indirect roles in mechanosensation. Using Caenorhabditis elegans as a model, here we have recorded a mechanosensitive conductance in a ciliated mechanosensory neuron in vivo. This conductance develops very rapidly upon mechanical stimulation with its latency and activation time constant reaching the range of microseconds, consistent with mechanical gating of the conductance. TRP-4, a TRPN (NOMPC) subfamily channel, is required for this conductance. Importantly, point mutations in the predicted pore region of TRP-4 alter the ion selectivity of the conductance. These results indicate that TRP-4 functions as an essential pore-forming subunit of a native mechanotransduction channel.
Kang
Lijun
L
Life Sciences Institute and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Gao
Jingwei
J
Schafer
William R
WR
Xie
Zhixiong
Z
Xu
X Z Shawn
XZ
D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000502:physiology*; D008465:Mechanoreceptors / Q000737:chemistry / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D005810:Multigene Family; D021122:Protein Subunits / Q000737:chemistry / Q000502:physiology*; D050052:TRPC Cation Channels / Q000737:chemistry / Q000502:physiology*; D050051:Transient Receptor Potential Channels / Q000737:chemistry / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D021122:Protein Subunits; C509780:TRP-4 channel, C elegans; D050052:TRPC Cation Channels; D050051:Transient Receptor Potential Channels