αCaMKII binding to the C‐terminal tail of NMDA receptor subunit NR2A and its modulation by autophosphorylation

FEBS Letters

Schrama, L.H.¹  van Dalen, J.J.W.¹  Cattabeni, F.²  Gispen, W.H.¹  Di Luca, M.²  Gardoni, F.² 

[1] Rudolf Magnus Institute of Neuroscience, University of Utrecht, Utrecht, The Netherlands;Institute of Pharmacological Sciences, University of Milano, via Balzaretti 9, 20133 Milano, Italy

关键词: Rat;    Hippocampus;    Phosphorylation;    Post-synaptic density;    CaMKII;    GST fusion protein;    CaMKII;    calcium/calmodulin-dependent protein kinase II;    GST;    glutathione S-transferase;    LTD;    long-term depression;    LTP;    long-term potentiation;    NMDA;    N-methyl-D-aspartate;    PMSF;    phenyl-methyl-sulfonyl fluoride;    PSD;    post-synaptic density;    SDS;    sodium dodecyl sulfate;   

DOI  :  10.1016/S0014-5793(99)00985-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), a multifunctional, widely distributed enzyme, is enriched in post-synaptic densities (PSDs). Here, we demonstrate that CaMKII binds to a discrete C-terminal region of the NR2A subunit of NMDA receptors and promotes the phosphorylation of a Ser residue of this NMDA receptor subunit. Glutathione S-transferase (GST)-NR2A(1349-1464) binds native CaMKII from solubilised hippocampal PSDs in ‘pull-out’ and overlay experiments and this binding is competed by recombinant αCaMKII(1-315). The longer GST-NR2A(1244-1464), although containing the CaMKII phosphosite Ser-1289, binds the kinase with a lower efficacy. CaMKII association to NR2A(1349-1464) is positively modulated by kinase autophosphorylation in the presence of Ca²⁺/calmodulin. These data provide direct evidence for a mechanism modulating the synaptic strength.

【 授权许可】

Unknown