title: Identification of a serotonin receptor coupled to adenylyl cyclase involved in learning-related heterosynaptic facilitation in Aplysia.
abstract: Serotonin (5-HT) plays a critical role in modulating synaptic plasticity in the marine mollusc Aplysia and in the mammalian nervous system. In Aplysia sensory neurons, 5-HT can activate several signal cascades, including PKA and PKC, presumably via distinct types of G protein-coupled receptors. However, the molecular identities of these receptors have not yet been identified. We here report the cloning and functional characterization of a 5-HT receptor that is positively coupled to adenylyl cyclase in Aplysia neurons. The cloned receptor, 5-HT(apAC1), stimulates the production of cAMP in HEK293T cells and in Xenopus oocytes. Moreover, the knockdown of 5-HT(apAC1) expression by RNA interference blocked 5-HT-induced cAMP production in Aplysia sensory neurons and blocked synaptic facilitation in nondepressed or partially depressed sensory-to-motor neuron synapses. These data implicate 5-HT(apAC1) as a major modulator of learning related synaptic facilitation in the direct sensory to motor neuron pathway of the gill withdrawal reflex.
authors.affiliation: Department of Biological Sciences, National Creative Research Initiative Center for Memory and Institute of Molecular Biology and Genetics, College of Natural Sciences, Seoul National University, Gwanak-gu, Seoul 151-747, Korea.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Lee
authors.forename: Sun-Lim
authors.initials: SL
authors.lastname: Choi
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Hyoung
authors.initials: H
authors.lastname: Kim
authors.forename: Hyungju
authors.initials: H
authors.lastname: Park
authors.forename: Nuribalhae
authors.initials: N
authors.lastname: Lee
authors.forename: Sue-Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Yeon-Su
authors.initials: YS
authors.lastname: Chae
authors.forename: Deok-Jin
authors.initials: DJ
authors.lastname: Jang
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
authors.forename: Bong-Kiun
authors.initials: BK
authors.lastname: Kaang
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D023902:Chromosome Pairing / Q000502:physiology*; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007858:Learning / Q000502:physiology*; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D010802:Phylogeny; D011985:Receptors, Serotonin / Q000145:classification / Q000235:genetics / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012701:Serotonin / Q000494:pharmacology; D014162:Transfection; D014982:Xenopus laevis
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases
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