LTP expression mediated by autonomous activity of GluN2B-bound CaMKII.

Autor:	Rumian NL; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Barker CM; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Larsen ME; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Tullis JE; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Freund RK; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Taslimi A; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Coultrap SJ; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Tucker CL; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Dell'Acqua ML; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Bayer KU; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: ulli.bayer@cuanschutz.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Oct 22; Vol. 43 (10), pp. 114866. Date of Electronic Publication: 2024 Oct 11.
DOI:	10.1016/j.celrep.2024.114866
Abstrakt:	Learning and memory are thought to require the induction and maintenance of long-term potentiation (LTP) of synaptic strength. LTP induction requires the Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) but for structural rather than enzymatic functions. We show that the relevant structural function is regulated by CaMKII binding to the NMDA-type glutamate receptor subunit GluN2B. This binding directly generates Ca 2+ -independent autonomous CaMKII activity, and we show that this enzymatic activity is dispensable for LTP induction (within 5 min) but required for a subsequent LTP phase (within 15 min). This requirement for CaMKII activity provides an objective temporal definition for the intermediary phase of LTP expression. Later LTP maintenance may still require structural functions of GluN2B-bound CaMKII but not the resulting enzymatic CaMKII activity or their co-condensation. Thus, autonomous CaMKII activity mediates post-induction LTP but (1) via GluN2B binding, not T286 autophosphorylation, and (2) during the intermediary expression phase rather than for long-term maintenance. Competing Interests: Declaration of interests The Regents of the University of Colorado have filed a patent application, with N.L.R., M.E.L., J.E.T., S.J.C., and K.U.B. in the list of inventors, that includes findings reported in this manuscript. K.U.B. is co-founder and board member of Neurexis Therapeutics, a company that seeks to develop a CaMKII inhibitor into a therapeutic drug for cerebral ischemia. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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