Regulation of calcium/calmodulin-dependent protein kinase II docking to N-methyl-D-aspartate receptors by calcium/calmodulin and α-actinin

A. Soren Leonard, K. Ulrich Bayer, Michelle A. Merrill, Indra A. Lim, Madeline A. Shea, Howard Schulman, Johannes W Hell

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Ca2+ influx through the N-methyl-D-aspartate (NMDA)-type glutamate receptor leads to activation and postsynaptic accumulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and ultimately to long term potentiation, which is thought to be the physiological correlate of learning and memory. The NMDA receptor also serves as a CaMKII docking site in dendritic spines with high affinity binding sites located on its NR1 and NR2B subunits. We demonstrate that high affinity binding of CaMKII to NR1 requires autophosphorylation of Thr286. This autophosphorylation reduces the off rate to a level (t1/2 = ∼23 min) that is similar to that observed for dissociation of the T286D mutant CaMKII (t1/2 = ∼30 min) from spines after its glutamate-induced accumulation (Shen, K., Teruel, M. N., Connor, J. H., Shenolikar, S., and Meyer, T. (2000) Nat. Neurosci. 3, 881-886). CaMKII as well as the previously identified NR1 binding partners calmodulin and α-actinin bind to the short C-terminal portion of the CO region of NR1. Like Ca2+/calmodulin, autophosphorylated CaMKII competes with α-actinin-2 for binding to NR1. We conclude that the NR1 C0 region is a key site for recruiting CaMKII to the postsynaptic site, where it may act in concert with calmodulin to modulate the stimulatory role of α-actinin interaction with the NMDA receptor.

Original languageEnglish (US)
Pages (from-to)48441-48448
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number50
DOIs
StatePublished - Dec 13 2002
Externally publishedYes

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Actinin
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Calmodulin
N-Methyl-D-Aspartate Receptors
Calcium
Dendritic Spines
Long-Term Potentiation
Glutamate Receptors
N-Methylaspartate
Carbon Monoxide
Glutamic Acid
Spine
Chemical activation
Binding Sites
Learning
Data storage equipment

ASJC Scopus subject areas

  • Biochemistry

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Regulation of calcium/calmodulin-dependent protein kinase II docking to N-methyl-D-aspartate receptors by calcium/calmodulin and α-actinin. / Leonard, A. Soren; Bayer, K. Ulrich; Merrill, Michelle A.; Lim, Indra A.; Shea, Madeline A.; Schulman, Howard; Hell, Johannes W.

In: Journal of Biological Chemistry, Vol. 277, No. 50, 13.12.2002, p. 48441-48448.

Research output: Contribution to journalArticle

Leonard, A. Soren ; Bayer, K. Ulrich ; Merrill, Michelle A. ; Lim, Indra A. ; Shea, Madeline A. ; Schulman, Howard ; Hell, Johannes W. / Regulation of calcium/calmodulin-dependent protein kinase II docking to N-methyl-D-aspartate receptors by calcium/calmodulin and α-actinin. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 50. pp. 48441-48448.
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AU - Bayer, K. Ulrich

AU - Merrill, Michelle A.

AU - Lim, Indra A.

AU - Shea, Madeline A.

AU - Schulman, Howard

AU - Hell, Johannes W

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