TRPswitch-A Step-Function Chemo-optogenetic Ligand for the Vertebrate TRPA1 Channel.

ABSTRACT: Chemo-optogenetics has produced powerful tools for optical control of cell activity, but current tools suffer from a variety of limitations including low unitary conductance, the need to modify the target channel, or the inability to control both on and off switching. Using a zebrafish behavior-based screening strategy, we discovered "TRPswitch", a photoswitchable nonelectrophilic ligand scaffold for the transient receptor potential ankyrin 1 (TRPA1) channel. TRPA1 exhibits high unitary channel conductance, making it an ideal target for chemo-optogenetic tool development. Key molecular determinants for the activity of TRPswitch were elucidated and allowed for replacement of the TRPswitch azobenzene with a next-generation azoheteroarene. The TRPswitch compounds enable reversible, repeatable

SUBMITTER: Lam PY 

PROVIDER: S-EPMC8011302 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature