Mechanisms for Generating the Autonomous cAMP-Dependent Protein Kinase Required for Long-Term Facilitation in Aplysia
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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.
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The PKA and ERK cascades are necessary to induce long-term synaptic facilitation (LTF) in Aplysia.
“Two biochemical cascades required for LTF are those that mediate activation of protein kinase A (PKA)12–15 and the MAP kinase isoform termed extracellular signal-regulated kinase (ERK)16–18.”
From Computational design of enhanced learning protocols (2012) · cites this paper as [15]
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- Authors
- Chain, D. G., Casadio, A., Schacher, S., Hegde, A. N., Valbrun, M., Yamamoto, N., Goldberg, A. L., Bartsch, D., Kandel, E. R., & Schwartz, J. H.
- Affiliations
- Columbia University (US)
- Harvard University (US)
- Corresponding author
- Schwartz, James H
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 22
- Issue
- 1
- Pages
- 147-156
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2021608362
- Cited by
- 186
- References
- 69
- Citations by year
- 2025: 2 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 6 · 2016: 8 · 2015: 10 · 2014: 14 · 2013: 5 · 2012: 6
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01gm032099-14)
- National Institute of Mental Health (MH-48850, R01MH048850)
- National Institute of General Medical Sciences (GM 32099)
- National Institute of Neurological Disorders and Stroke (NS-29255)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- protein kinase A, long-term facilitation, Aplysia, ubiquitin-proteasome degradation, catalytic subunit, serotonin, synaptic plasticity, lactacystin, allosteric regulation, sensory neurons
- MeSH terms
- Cyclic AMP, Animals, Aplysia, Cattle, Cysteine Endopeptidases, Injections, Multienzyme Complexes, Neurons, Afferent, Peptide Fragments, Serotonin, Ubiquitins, Long-Term Potentiation, Cyclic AMP-Dependent Protein Kinases, Proteasome Endopeptidase Complex
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