Protection of α-CaMKII from Dephosphorylation by GluN2B Subunit of NMDA Receptor Is Abolished by Mutation of Glu96 or His282 of α-CaMKII.
Interaction of CaMKII and the GluN2B subunit of NMDA receptor is essential for synaptic plasticity events such as LTP. Synaptic targeting of CaMKII and regulation of its biochemical functions result from this interaction. GluN2B binding to the T-site of CaMKII leads to changes in substrate binding and catalytic parameters and inhibition of its own dephosphorylation. We find that CaMKIINα, a natural inhibitor that binds to the T-site of CaMKII, also causes inhibition of dephosphorylation of CaMKII similar to GluN2B. Two residues on α-CaMKII, Glu96 and His282, are involved in the inhibition of CaMKII dephosphorylation exerted by binding of GluN2B. E96A-α-CaMKII is known to be defective in GluN2B-induced catalytic modulation. Data presented here show that, in both E96A and H282A mutants of α-CaMKII, GluN2B-induced inhibition of dephosphorylation is impaired.
Molecular Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud, P. O., Thiruvananthapuram-695014, Kerala, India.
Madhavan
M
Mayadevi
Molecular Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud, P. O., Thiruvananthapuram-695014, Kerala, India.
Kesavan
K
Lakshmi
Molecular Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud, P. O., Thiruvananthapuram-695014, Kerala, India.
Sudarsana Devi
SD
Suma Priya
Molecular Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud, P. O., Thiruvananthapuram-695014, Kerala, India.
Sebastian
S
John
Molecular Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud, P. O., Thiruvananthapuram-695014, Kerala, India.
Ramakrishnapillai V
RV
Omkumar
D001665:Binding Sites; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics* / Q000378:metabolism; D005973:Glutamine / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2