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

Full text not available from this repository.

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:	Schools > Medicine Research Institutes & Centres > Neuroscience and Mental Health Research Institute (NMHII)
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

Citation Data

Cited 30 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item