Phosphorylation-dependent subcellular translocation of a Ca2+/calmodulin-dependent protein kinase produces an autonomous enzyme in Aplysia neurons.
Open accessAbstract
We have shown previously that the subcellular distribution of a major calmodulin-binding protein is altered under conditions causing increased synthesis of cAMP in Aplysia neurons (Saitoh, T., and J. H. Schwartz, 1983, Proc. Natl. Acad. Sci. USA, 80:6708-6712). We now provide evidence that this Mr 55,000 protein is a subunit of a Ca2+/calmodulin-dependent kinase: (a) both the Mr 55,000 calmodulin-binding protein and kinase activity are loosely attached to the membrane-cytoskeletal complex; (b) both kinase activity and the Mr 55,000 protein are translocated from the membrane-cytoskeleton complex to the cytoplasm under conditions that cause the change in the subcellular distribution of the Mr 55,000 calmodulin-binding protein; and (c) calmodulin-binding activity of the Mr 55,000 protein and the ability to carry out the Ca2+/calmodulin-dependent phosphorylation of synapsin I are purified in parallel. The subcellular localization of the Ca2+/calmodulin-dependent protein kinase appears to be under control of two second messengers: Ca2+ and cAMP. We find that the Mr 55,000 subunit is phosphorylated when the extracted membrane-cytoskeleton complex is incubated with Ca2+, calmodulin, and ATP, with the concomitant release of this phosphorylated peptide from the complex. Previously, we had found that, when translocation occurs in extracts in the presence of cAMP and ATP (but in the absence of Ca2+), there was no detectable phosphorylation of the Mr 55,000 subunit itself. The subcellular distribution of the subunit thus appears to be influenced by (a) cAMP-dependent phosphorylation, which, we infer, modifies some as yet unidentified structural component, causing the release of the enzyme; and (b) Ca2+/calmodulin-dependent phosphorylation of the Mr 55,000 subunit. These studies also suggest that phosphorylation has an important regulatory consequence: during the Ca2+/calmodulin-dependent translocation of the Mr 55,000 subunit, the kinase appears to be activated, becoming independent of added Ca2+/calmodulin.
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CaMKII becomes independent of Ca2+ (autonomous) after autophosphorylation.
“it was not until the discovery of a Ca2+/calmodulin-dependent protein kinase, now referred to as CaMKII (9, 10), which became independent of Ca2+ (autonomous) after autophosphorylation (11–15)”
From Synaptic memory and CaMKII (2023) · cites this paper as [11]
In “Possible Activation of the Kinase” (p. 840), the authors report that the treated Aplysia kinase becomes independent of added Ca2+/calmodulin. They describe autophosphorylation as “one attractive idea” for how this happens, not an established cause, so the claim overstates that link. (LLM, conf=0.88)
Experimental — accuracy not yet measuredOnce activated by Ca2+, CaMKII enzymatic activity toward substrates remains after Ca2+ removal.
“Fourth, CaMKII has the intriguing property that once activated by Ca2+ the enzymatic activity toward substrates remains after Ca2+ removal (11–15).”
From Synaptic memory and CaMKII (2023) · cites this paper as [11]
The Fig. 4 and Table III passages report that an Aplysia kinase treated with Ca2+/calmodulin and ATP could subsequently phosphorylate synapsin I under Ca2+-free conditions. The claim omits the ATP-dependent treatment and presents this as a general property of CaMKII activity toward substrates, whereas the paper demonstrates it for synapsin I under those conditions. (LLM, conf=0.85)
Experimental — accuracy not yet measured
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“Fourth, CaMKII has the intriguing property that once activated by Ca 2 1 the enzymatic activity toward substrates remains after Ca 2 1 removal (11 – 15).”
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- Authors
- Saitoh, T., & Schwartz, J. H.
- Venue
- The Journal of cell biology
- Publisher
- Rockefeller University Press
- Published
- 1985-03-01
- Volume
- 100
- Issue
- 3
- Pages
- 835-842
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2113531
- OpenAlex
- W2102459797
- Cited by
- 259
- References
- 0
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 11 · 2012: 6
- FWCI
- 9.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 15834)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- subcellular translocation, phosphorylation, calmodulin-binding proteins, Aplysia neurons, cyclic AMP, second messengers, synapsin I phosphorylation, kinase activation, calmodulin
- MeSH terms
- Animals, Aplysia, Biological Transport, Active, Calmodulin-Binding Proteins, Cell Membrane, Cytoskeleton, Enzyme Activation, Molecular Weight, Synaptic Transmission, Neurons, Phosphoprotein Phosphatases, Phosphorylation, Protein Kinases, Serotonin, In Vitro Techniques
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