PUBLICATION
Ciliary localization of a light-activated neuronal GPCR shapes behavior
- Authors
- Winans, A.M., Friedmann, D., Stanley, C., Xiao, T., Liu, T.L., Chang, C.J., Isacoff, E.Y.
- ID
- ZDB-PUB-231017-63
- Date
- 2023
- Source
- Proceedings of the National Academy of Sciences of the United States of America 120: e2311131120e2311131120 (Journal)
- Registered Authors
- Isacoff, Ehud, Xiao, Tong
- Keywords
- VALopA, central pattern generator, cilium, opsin, zebrafish
- MeSH Terms
-
- Animals
- Cilia/physiology
- Neurons
- Opsins
- Receptors, G-Protein-Coupled*/physiology
- Rod Opsins
- Signal Transduction/physiology
- Zebrafish*
- PubMed
- 37844228 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Winans, A.M., Friedmann, D., Stanley, C., Xiao, T., Liu, T.L., Chang, C.J., Isacoff, E.Y. (2023) Ciliary localization of a light-activated neuronal GPCR shapes behavior. Proceedings of the National Academy of Sciences of the United States of America. 120:e2311131120e2311131120.
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 Gi-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 Gi-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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping