The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
CaMKII tethers to L-type Ca2 + channels, establishing a local and dedicated integrator of Ca2 + signals for facilitation
Open accessAbstract
Ca2+-dependent facilitation (CDF) of voltage-gated calcium current is a powerful mechanism for up-regulation of Ca2+ influx during repeated membrane depolarization. CDF of L-type Ca2+ channels (Cav1.2) contributes to the positive force–frequency effect in the heart and is believed to involve the activation of Ca2+/calmodulin-dependent kinase II (CaMKII). How CaMKII is activated and what its substrates are have not yet been determined. We show that the pore-forming subunit α1C (Cavα1.2) is a CaMKII substrate and that CaMKII interaction with the COOH terminus of α1C is essential for CDF of L-type channels. Ca2+ influx triggers distinct features of CaMKII targeting and activity. After Ca2+-induced targeting to α1C, CaMKII becomes tightly tethered to the channel, even after calcium returns to normal levels. In contrast, activity of the tethered CaMKII remains fully Ca2+/CaM dependent, explaining its ability to operate as a calcium spike frequency detector. These findings clarify the molecular basis of CDF and demonstrate a novel enzymatic mechanism by which ion channel gating can be modulated by activity.
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Cites
The molecular basis of CaMKII function in synaptic and behavioural memory
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Self-citationCalmodulin Trapping by Calcium-Calmodulin-Dependent Protein Kinase
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Self-citationModulation of L-type calcium channels in Alzheimer’s disease: A potential therapeutic target
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Metadata
- Authors
- Hudmon, A., Schulman, H., Kim, J., Maltez, J. M., Tsien, R. W., & Pitt, G. S.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2005-11-07
- Volume
- 171
- Issue
- 3
- Pages
- 537-547
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2168556429
- Cited by
- 344
- References
- 5
- FWCI
- 6.22
- Type
- journal article
- Language
- en
- Open access
- green
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