Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation.
Serotonin (5-hydroxytryptamine, 5-HT) is, without doubt, the neurotransmitter for which the number of receptors is the highest. Fifteen genes encoding functional 5-HT receptors have been cloned in mammalian brain. 5-HT(3) receptors are ionotropic receptors, whereas all the others are metabotropic G-protein-coupled receptors (GPCRs). 5-HT receptor diversity is further increased by post-genomic modifications, such as alternative splicing (up to 10 splice variants for the 5-HT(4) receptor) or by mRNA editing in the case of 5-HT(2C) receptors. The cellular and behavioral implications of 5-HT(2C) receptor editing are of great physiological importance. Signaling of 5-HT receptors involves a great variety of pathways, but only some of these have been demonstrated in neurons. The classical view of neurotransmitter receptors localized within the synaptic cleft cannot be applied to 5-HT receptors, which are mostly (but not exclusively) localized at extra-synaptic locations either pre- or post-synaptically. 5-HT receptors are engaged in pre- or post-synaptic complexes composed of many GPCR-interacting proteins. The functions of these proteins are starting to be revealed. These proteins have been implicated in targeting, trafficking to or from the membrane, desensitization, and fine-tuning of signaling.
Bockaert
Joël
J
CNRS, UMR5203, Montpellier, F-34094, France. Joel.Bockaert@igf.cnrs.fr
Claeysen
Sylvie
S
Bécamel
Carine
C
Dumuis
Aline
A
Marin
Philippe
P
D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D006801:Humans; D005810:Multigene Family / Q000502:physiology*; D011985:Receptors, Serotonin / Q000096:biosynthesis* / Q000235:genetics; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
D011985:Receptors, Serotonin; D012701:Serotonin