Identification of a serotonin receptor coupled to adenylyl cyclase involved in learning-related heterosynaptic facilitation in Aplysia.
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.
Lee
Yong-Seok
YS
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.
Choi
Sun-Lim
SL
Lee
Seung-Hee
SH
Kim
Hyoung
H
Park
Hyungju
H
Lee
Nuribalhae
N
Lee
Sue-Hyun
SH
Chae
Yeon-Su
YS
Jang
Deok-Jin
DJ
Kandel
Eric R
ER
Kaang
Bong-Kiun
BK
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
D011985:Receptors, Serotonin; D012701:Serotonin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases
J Neurosci. 1989 Dec;9(12):4200-13
2592997
Learn Mem. 2003 Sep-Oct;10(5):373-86
14557610
J Neurosci. 2005 Sep 28;25(39):9037-45
16192395
J Neurosci. 1998 Aug 1;18(15):5586-93
9671650
J Neurochem. 2006 Sep;98(6):1985-98
16945110
Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16513-8
15545605
Neuron. 1993 Mar;10(3):427-35
8384857
Proc Natl Acad Sci U S A. 1987 Jun;84(12):4332-6
3473504
Proc Natl Acad Sci U S A. 1990 Mar;87(5):2040-4
2155432
Pharmacol Biochem Behav. 2002 Apr;71(4):533-54
11888546
Neuron. 1997 Jun;18(6):899-912
9208858
Comp Biochem Physiol A Mol Integr Physiol. 2001 Apr;128(4):791-804
11282322
FEBS Lett. 1996 Mar 4;381(3):233-6
8601462
Neuron. 2009 Feb 26;61(4):527-40
19249274
Neuropharmacology. 1994 Mar-Apr;33(3-4):319-24
7984268
Neuron. 2006 Mar 2;49(5):707-18
16504946
Pharmacol Rev. 1994 Jun;46(2):157-203
7938165
Learn Mem. 2001 Jul-Aug;8(4):220-6
11533225
J Neurochem. 1999 Jan;72(1):58-65
9886054
Biol Bull. 2006 Jun;210(3):174-91
16801493
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18602-7
19017802
EMBO Rep. 2004 Dec;5(12):1176-80
15550931
J Neurophysiol. 1989 Sep;62(3):665-79
2549212
J Biol Chem. 1994 Jan 28;269(4):2790-5
7507928
Mol Brain. 2008 Jun 17;1:3
18803855
J Neurochem. 2002 Jan;80(2):335-45
11902124
Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11481-5
1333612
Science. 1991 Dec 20;254(5039):1811-3
1662413
Cell. 2006 Dec 29;127(7):1453-67
17190607
J Biol Chem. 1993 Oct 25;268(30):22273-6
8226735
J Neurophysiol. 2006 Apr;95(4):2713-20
16236785
Neuron. 1992 Sep;9(3):479-89
1355977
Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317
7984267
J Neurophysiol. 1990 Sep;64(3):978-90
2172477
Cell. 1995 Oct 20;83(2):195-206
7585937
Science. 2001 Nov 2;294(5544):1030-8
11691980
Proc Natl Acad Sci U S A. 1984 Dec;81(24):7956-60
6096869
J Neurophysiol. 2003 Mar;89(3):1440-55
12611939
Science. 1986 Dec 5;234(4781):1249-54
3775383
J Neurosci. 1996 Jan 15;16(2):425-35
8551327
Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1829-34
10677541
Brain Res Bull. 2003 Apr 15;60(1-2):73-9
12725895
J Med Chem. 2000 Feb 10;43(3):342-5
10669560
Science. 1976 Dec 10;194(4270):1178-81
186870
Brain Res. 1980 Feb 17;184(1):163-77
7357415
J Neurosci. 1983 Dec;3(12):2403-13
6655493