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Brain spectrin binding to the NMDA receptor is regulated by phosphorylation, calcium and calmodulin
Author(s) -
Wechsler Aharon,
Teichberg Vivian I.
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.14.3931
Subject(s) - biology , calmodulin , spectrin , phosphorylation , nmda receptor , calcium binding protein , calcium , microbiology and biotechnology , receptor , calmodulin binding proteins , biochemistry , cytoskeleton , medicine , cell , enzyme
The N ‐methyl‐D‐aspartate receptor (NMDA‐R) and brain spectrin, a protein that links membrane proteins to the actin cytoskeleton, are major components of post‐synaptic densities (PSDs). Since the activity of the NMDA‐R channel is dependent on the integrity of actin and leads to calpain‐mediated spectrin breakdown, we have investigated whether the actin‐binding spectrin may interact directly with NMDA‐Rs. Spectrin is reported here to interact selectively in vitro with the C‐terminal cytoplasmic domains of the NR1a, NR2A and NR2B subunits of the NMDA‐R but not with that of the AMPA receptor GluR1. Spectrin binds at NR2B sites distinct from those of α‐actinin‐2 and members of the PSD95/SAP90 family. The spectrin–NR2B interactions are antagonized by Ca 2+ and fyn‐mediated NR2B phosphorylation, but not by Ca 2+ /calmodulin (CaM) or by Ca 2+ /CaM‐dependent protein kinase II‐mediated NR2B phosphorylation. The spectrin–NR1 interactions are unaffected by Ca 2+ but inhibited by CaM and by protein kinase A‐ and C‐mediated phosphorylations of NR1. Finally, in rat synaptosomes, both spectrin and NR2B are loosened from membranes upon addition of physiological concentrations of calcium ions. The highly regulated linkage of the NMDA‐R to spectrin may underlie the morphological changes that occur in neuronal dendrites concurrently with synaptic activity and plasticity.