LTP induction by structural rather than enzymatic functions of CaMKII

Jonathan E. Tullis, Matthew E. Larsen, Nicole L. Rumian, Ronald K. Freund, Emma E. Boxer, Carolyn Nicole Brown, Steven J. Coultrap, Howard Schulman, Jason Aoto, Mark L. Dell’Acqua and K. Ulrich Bayer ()
Additional contact information
Jonathan E. Tullis: University of Colorado Anschutz Medical Campus
Matthew E. Larsen: University of Colorado Anschutz Medical Campus
Nicole L. Rumian: University of Colorado Anschutz Medical Campus
Ronald K. Freund: University of Colorado Anschutz Medical Campus
Emma E. Boxer: University of Colorado Anschutz Medical Campus
Carolyn Nicole Brown: University of Colorado Anschutz Medical Campus
Steven J. Coultrap: University of Colorado Anschutz Medical Campus
Howard Schulman: Stanford University School of Medicine
Jason Aoto: University of Colorado Anschutz Medical Campus
Mark L. Dell’Acqua: University of Colorado Anschutz Medical Campus
K. Ulrich Bayer: University of Colorado Anschutz Medical Campus

Nature, 2023, vol. 621, issue 7977, 146-153

Abstract: Abstract Learning and memory are thought to require hippocampal long-term potentiation (LTP), and one of the few central dogmas of molecular neuroscience that has stood undisputed for more than three decades is that LTP induction requires enzymatic activity of the Ca2+/calmodulin-dependent protein kinase II (CaMKII)1–3. However, as we delineate here, the experimental evidence is surprisingly far from conclusive. All previous interventions inhibiting enzymatic CaMKII activity and LTP4–8 also interfere with structural CaMKII roles, in particular binding to the NMDA-type glutamate receptor subunit GluN2B9–14. Thus, we here characterized and utilized complementary sets of new opto-/pharmaco-genetic tools to distinguish between enzymatic and structural CaMKII functions. Several independent lines of evidence demonstrated LTP induction by a structural function of CaMKII rather than by its enzymatic activity. The sole contribution of kinase activity was autoregulation of this structural role via T286 autophosphorylation, which explains why this distinction has been elusive for decades. Directly initiating the structural function in a manner that circumvented this T286 role was sufficient to elicit robust LTP, even when enzymatic CaMKII activity was blocked.

Date: 2023
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-023-06465-y Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:621:y:2023:i:7977:d:10.1038_s41586-023-06465-y

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-023-06465-y

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().