Ciliary localization of a light-activated neuronal GPCR shapes behavior.

janelia7_blocks-janelia7_biblio_header | block

Proceedings of the National Academy of Sciences of the USA. 2023 Oct 16;120(43):e2311131120. doi: 10.1073/pnas.2311131120

View Article on

Winans AM, Friedmann D, Stanley C, Xiao T, Liu T, Chang CJ, Isacoff EY

janelia7_blocks-janelia7_biblio_abstract | block

Abstract

Many neurons in the central nervous system produce a single primary cilium that serves as a specialized signaling organelle. Several neuromodulatory G-protein-coupled receptors (GPCRs) localize to primary cilia in neurons, although it is not understood how GPCR signaling from the cilium impacts circuit function and behavior. We find that the vertebrate ancient long opsin A (VALopA), a G-coupled GPCR extraretinal opsin, targets to cilia of zebrafish spinal neurons. In the developing 1-d-old zebrafish, brief light activation of VALopA in neurons of the central pattern generator circuit for locomotion leads to sustained inhibition of coiling, the earliest form of locomotion. We find that a related extraretinal opsin, VALopB, is also G-coupled, but is not targeted to cilia. Light-induced activation of VALopB also suppresses coiling, but with faster kinetics. We identify the ciliary targeting domains of VALopA. Retargeting of both opsins shows that the locomotory response is prolonged and amplified when signaling occurs in the cilium. We propose that ciliary localization provides a mechanism for enhancing GPCR signaling in central neurons.

Main Menu (Mobile)- Block

Main Menu - Block

Ciliary localization of a light-activated neuronal GPCR shapes behavior.

Abstract

PMID: 37844228 [PubMed - indexed for MEDLINE]