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CaMKII translocation requires local NMDA receptor-mediated Ca2+ signaling

Thalhammer, Agnes, Rudhard, York, Tigaret, Cezar M. ORCID: https://orcid.org/0000-0001-5848-6697, Volynski, Kirill E., Rusakov, Dmitri A. and Schoepfer, Ralf 2006. CaMKII translocation requires local NMDA receptor-mediated Ca2+ signaling. EMBO Journal 25 (24) , pp. 5873-5883. 10.1038/sj.emboj.7601420

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Abstract

Excitatory synaptic transmission and plasticity are critically modulated by N‐methyl‐D‐aspartate receptors (NMDARs). Activation of NMDARs elevates intracellular Ca2+ affecting several downstream signaling pathways that involve Ca2+/calmodulin‐dependent protein kinase II (CaMKII). Importantly, NMDAR activation triggers CaMKII translocation to synaptic sites. NMDAR activation failed to induce Ca2+ responses in hippocampal neurons lacking the mandatory NMDAR subunit NR1, and no EGFP‐CaMKIIα translocation was observed. In cells solely expressing Ca2+‐impermeable NMDARs containing NR1N598R‐mutant subunits, prolonged NMDA application elevated internal Ca2+ to the same degree as in wild‐type controls, yet failed to translocate CaMKIIα. Brief local NMDA application evoked smaller Ca2+ transients in dendritic spines of mutant compared to wild‐type cells. CaMKIIα mutants that increase binding to synaptic sites, namely CaMKII‐T286D and CaMKII‐TT305/306VA, rescued the translocation in NR1N598R cells in a glutamate receptor‐subtype‐specific manner. We conclude that CaMKII translocation requires Ca2+ entry directly through NMDARs, rather than other Ca2+ sources activated by NMDARs. Together with the requirement for activated, possibly ligand‐bound, NMDARs as CaMKII binding partners, this suggests that synaptic CaMKII accumulation is an input‐specific signaling event.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Nature Publishing Group: EMBO
ISSN: 0261-4189
Date of First Compliant Deposit: 14 January 2020
Date of Acceptance: 11 October 2006
Last Modified: 26 Oct 2022 08:52
URI: https://orca.cardiff.ac.uk/id/eprint/128528

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