Deorphanization of novel biogenic amine-gated ion channels identifies a new serotonin receptor for learning.

Morud J, Hardege I, Liu H, Wu T, Choi MK, Basu S, Zhang Y, Schafer WR

Curr. Biol. 31 (19) 4282-4292.e6 [2021-10-11; online 2021-08-12]

Pentameric ligand-gated ion channels (LGICs) play conserved, critical roles in both excitatory and inhibitory synaptic transmission and can be activated by diverse neurochemical ligands. We have performed a characterization of orphan channels from the nematode C. elegans, identifying five new monoamine-gated LGICs with diverse functional properties and expression postsynaptic to aminergic neurons. These include polymodal anion channels activated by both dopamine and tyramine, which may mediate inhibitory transmission by both molecules in vivo. Intriguingly, we also find that a novel serotonin-gated cation channel, LGC-50, is essential for aversive olfactory learning of pathogenic bacteria, a process known to depend on serotonergic neurotransmission. Remarkably, the redistribution of LGC-50 to neuronal processes is modulated by olfactory conditioning, and lgc-50 point mutations that cause misregulation of receptor membrane expression interfere with olfactory learning. Thus, the intracellular trafficking and localization of these receptors at synapses may represent a molecular cornerstone of the learning mechanism.

Integrated Microscopy Technologies Gothenburg [Service]

PubMed 34388373

DOI 10.1016/j.cub.2021.07.036

Crossref 10.1016/j.cub.2021.07.036

pmc: PMC8536830
pii: S0960-9822(21)00991-X