title: The two regulatory subunits of aplysia cAMP-dependent protein kinase mediate distinct functions in producing synaptic plasticity.
abstract: Activation of the cAMP-dependent protein kinase (PKA) is critical for both short- and long-term facilitation in Aplysia sensory neurons. There are two types of the kinase, I and II, differing in their regulatory (R) subunits. We cloned Aplysia RII; RI was cloned previously. Type I PKA is mostly soluble in the cell body whereas type II is enriched at nerve endings where it is bound to two prominent A kinase-anchoring-proteins (AKAPs). Disruption of the binding of RII to AKAPs by Ht31, an inhibitory peptide derived from a human thyroid AKAP, prevents both the short- and the long-term facilitation produced by serotonin (5-HT). During long-term facilitation, RII is transcriptionally upregulated; in contrast, the amount of RI subunits decreases, and previous studies have indicated that the decrease is through ubiquitin-proteosome-mediated proteolysis. Experiments with antisense oligonucleotides injected into the sensory neuron cell body show that the increase in RII protein is essential for the production of long-term facilitation. Using synaptosomes, we found that 5-HT treatment causes RII protein to increase at nerve endings. In addition, using reverse transcription-PCR, we found that RII mRNA is transported from the cell body to nerve terminals. Our results suggest that type I operates in the nucleus to maintain cAMP response element-binding protein-dependent gene expression, and type II PKA acts at sensory neuron synapses phosphorylating proteins to enhance release of neurotransmitter. Thus, the two types of the kinase have distinct but complementary functions in the production of facilitation at synapses of an identified neuron.
authors.affiliation: Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, New York, New York 10032, USA.
authors.forename: Jinming
authors.initials: J
authors.lastname: Liu
authors.forename: Jiang-Yuan
authors.initials: JY
authors.lastname: Hu
authors.forename: Samuel
authors.initials: S
authors.lastname: Schacher
authors.forename: James H
authors.initials: JH
authors.lastname: Schwartz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000187:drug effects / Q000201:enzymology*; D001483:Base Sequence; D003001:Cloning, Molecular; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D017952:Ganglia, Invertebrate / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010802:Phylogeny; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012701:Serotonin / Q000494:pharmacology; D013569:Synapses / Q000201:enzymology / Q000378:metabolism*
chemical_list: D016376:Oligonucleotides, Antisense; D021122:Protein Subunits; D012333:RNA, Messenger; D012701:Serotonin; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases