Competitive binding of alpha-actinin and calmodulin to the NMDA receptor

M Wyszynski; J Lin; A Rao; E Nigh; A H Beggs; A M Craig; M Sheng

doi:10.1038/385439a0

Competitive binding of alpha-actinin and calmodulin to the NMDA receptor

Nature. 1997 Jan 30;385(6615):439-42. doi: 10.1038/385439a0.

Authors

M Wyszynski¹, J Lin, A Rao, E Nigh, A H Beggs, A M Craig, M Sheng

Affiliation

¹ Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02114, USA.

PMID: 9009191
DOI: 10.1038/385439a0

Abstract

The mechanisms by which neurotransmitter receptors are immobilized at postsynaptic sites in neurons are largely unknown. The activity of NMDA (N-methyl-D-aspartate) receptors is mechanosensitive and dependent on the integrity of actin, suggesting a functionally important interaction between NMDA receptors and the postsynaptic cytoskeleton. alpha-Actinin-2, a member of the spectrin/dystrophin family of actin-binding proteins, is identified here as a brain postsynaptic density protein that colocalizes in dendritic spines with NMDA receptors and the putative NMDA receptor-clustering molecule PSD-95. alpha-Actinin-2 binds by its central rod domain to the cytoplasmic tail of both NR1 and NR2B subunits of the NMDA receptor, and can be immunoprecipitated with NMDA receptors and PSD-95 from rat brain. Intriguingly, NR1-alpha-actinin binding is directly antagonized by Ca2+/calmodulin. Thus alpha-actinin may play a role in both the localization of NMDA receptors and their modulation by Ca2+.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Actins / metabolism*
Amino Acid Sequence
Animals
Binding Sites
Binding, Competitive
Brain / metabolism
Calmodulin / metabolism*
Cells, Cultured
Disks Large Homolog 4 Protein
Hippocampus / cytology
Humans
Intracellular Signaling Peptides and Proteins
Kv1.4 Potassium Channel
Membrane Proteins
Molecular Sequence Data
Nerve Tissue Proteins / metabolism
Neurons / metabolism
Potassium Channels / metabolism
Potassium Channels, Voltage-Gated*
Rats
Receptors, N-Methyl-D-Aspartate / genetics
Receptors, N-Methyl-D-Aspartate / metabolism*
Recombinant Fusion Proteins / metabolism

Substances

Actins
Calmodulin
Disks Large Homolog 4 Protein
Dlg4 protein, rat
Intracellular Signaling Peptides and Proteins
KCNA4 protein, human
Kcna4 protein, rat
Kv1.4 Potassium Channel
Membrane Proteins
Nerve Tissue Proteins
Potassium Channels
Potassium Channels, Voltage-Gated
Receptors, N-Methyl-D-Aspartate
Recombinant Fusion Proteins
postsynaptic density proteins