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

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

doi:10.1074/jbc.M205164200

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

Journal article

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Peer reviewed

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

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

The Journal of biological chemistry, Vol.277(50), pp.48441-48448

12/13/2002

DOI: 10.1074/jbc.M205164200

PMID: 12379661

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Abstract

Ca(2+) influx through the N-methyl-d-aspartate (NMDA)-type glutamate receptor leads to activation and postsynaptic accumulation of Ca(2+)/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 Thr(286). This autophosphorylation reduces the off rate to a level (t(12) = approximately 23 min) that is similar to that observed for dissociation of the T286D mutant CaMKII (t(12) = approximately 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 alpha-actinin bind to the short C-terminal portion of the C0 region of NR1. Like Ca(2+)/calmodulin, autophosphorylated CaMKII competes with alpha-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 alpha-actinin interaction with the NMDA receptor.

Phosphorylation

Animals

Calmodulin - metabolism

Calcium - metabolism

Receptors, N-Methyl-D-Aspartate - metabolism

Protein Binding

Calcium-Calmodulin-Dependent Protein Kinase Type 2

Calcium-Calmodulin-Dependent Protein Kinases - metabolism

Actinin - metabolism

Spodoptera

Details

Title: Subtitle: Regulation of calcium/calmodulin-dependent protein kinase II docking to N-methyl-D-aspartate receptors by calcium/calmodulin and alpha-actinin
Creators: A Soren Leonard - Department of Pharmacology, University of Wisconsin, Madison 53706-1532, USA
K-Ulrich Bayer
Michelle A Merrill
Indra A Lim
Madeline A Shea
Howard Schulman
Johannes W Hell
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(50), pp.48441-48448
DOI: 10.1074/jbc.M205164200
PMID: 12379661
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: R01-NS35563 / NINDS NIH HHS AG00213 / NIA NIH HHS GM30179 / NIGMS NIH HHS
Language: English
Date published: 12/13/2002
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Biochemistry and Molecular Biology
Record Identifier: 9984024526602771

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