Competitive binding of alpha-actinin and calmodulin to the NMDA receptor.
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+.
Wyszynski
M
M
Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02114, USA.
Lin
J
J
Rao
A
A
Nigh
E
E
Beggs
A H
AH
Craig
A M
AM
Sheng
M
M
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051665:Kv1.4 Potassium Channel; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D000199:Actins; D002147:Calmodulin; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; C496977:KCNA4 protein, human; C496979:Kcna4 protein, rat; D051665:Kv1.4 Potassium Channel; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; C033652:postsynaptic density proteins