Serotonin stimulation of cAMP-dependent plasticity in Aplysia sensory neurons is mediated by calmodulin-sensitive adenylyl cyclase.
Calmodulin (CaM)-sensitive adenylyl cyclase (AC) in sensory neurons (SNs) in Aplysia has been proposed as a molecular coincidence detector during conditioning. We identified four putative ACs in Aplysia CNS. CaM binds to a sequence in the C1b region of AC-AplA that resembles the CaM-binding sequence in the C1b region of AC1 in mammals. Recombinant AC-AplA was stimulated by Ca(2+)/CaM. AC-AplC is most similar to the Ca(2+)-inhibited AC5 and AC6 in mammals. Recombinant AC-AplC was directly inhibited by Ca(2+), independent of CaM. AC-AplA and AC-AplC are expressed in SNs, whereas AC-AplB and AC-AplD are not. Knockdown of AC-AplA demonstrated that serotonin stimulation of cAMP-dependent plasticity in SNs is predominantly mediated by this CaM-sensitive AC. We propose that the coexpression of a Ca(2+)-inhibited AC in SNs, together with a Ca(2+)/CaM-stimulated AC, would enhance the associative requirement for coincident Ca(2+) influx and serotonin for effective stimulation of cAMP levels and initiation of plasticity mediated by AC-AplA.
Lin
Allison H
AH
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201-1559, USA.
Cohen
Jonathan E
JE
Wan
Qin
Q
Niu
Katelyn
K
Shrestha
Pragya
P
Bernstein
Steven L
SL
Abrams
Thomas W
TW
D000200:Action Potentials / Q000187:drug effects; D000262:Adenylyl Cyclases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism / Q000494:pharmacology; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D055785:Gene Knockdown Techniques; D015151:Immunoblotting; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity / Q000187:drug effects*; D010802:Phylogeny; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012701:Serotonin / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology
D002147:Calmodulin; D018076:DNA, Complementary; D018490:Serotonin Agents; D012701:Serotonin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium