Abstract
The formation of a persistently active cAMP-dependent protein kinase (PKA) is critical for establishing long-term synaptic facilitation (LTF) in Aplysia. The injection of bovine catalytic (C) subunits into sensory neurons is sufficient to produce protein synthesis-dependent LTF. Early in the LTF induced by serotonin (5-HT), an autonomous PKA is generated through the ubiquitin-proteasome-mediated proteolysis of regulatory (R) subunits. The degradation of R occurs during an early time window and appears to be a key function of proteasomes in LTF. Lactacystin, a specific proteasome inhibitor, blocks the facilitation induced by 5-HT, and this block is rescued by injecting C subunits. R is degraded through an allosteric mechanism requiring an elevation of cAMP coincident with the induction of a ubiquitin carboxy-terminal hydrolase.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Aplysia / metabolism
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Aplysia / physiology*
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Cattle
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Cyclic AMP / physiology
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Cyclic AMP-Dependent Protein Kinases / biosynthesis*
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Cyclic AMP-Dependent Protein Kinases / pharmacology
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Cysteine Endopeptidases / physiology
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Injections
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Long-Term Potentiation / physiology*
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Multienzyme Complexes / physiology
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Neurons, Afferent / drug effects
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Neurons, Afferent / physiology
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Proteasome Endopeptidase Complex
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Serotonin / pharmacology
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Ubiquitins / metabolism
Substances
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Multienzyme Complexes
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Peptide Fragments
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Ubiquitins
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Serotonin
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex