Protein kinase c activation modulates α-calmodulin kinase II bindiag to NR2A subunit of N-methyl-D-aspaatttt receptor complex
Protein kinase c activation modulates α-calmodulin kinase II bindiag to NR2A subunit of N-methyl-D-aspaatttt receptor complex
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DOI：
10.1074/jbc.m009922200
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发表时间：
2001-03-09
影响因子：
4.8
通讯作者：
Di Luca, M
中科院分区：
文献类型：
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作者：
Gardoni, F;Bellone, C;Di Luca, M
n -甲基- d -天冬氨酸（NMDA）受体亚基NR2具有扩展的细胞内c端结构域，通过该结构域，它们可以直接与大量参与突触聚集和信号传导的突触后密度（PSD）蛋白相互作用。我们之前已经证明psd相关的α -钙调蛋白激酶II（α CaMKII）与NR2A亚基的c端结构域具有高亲和力。在这里，我们发现NR2A细胞质尾的1412-1419残基对α CaMKII的结合至关重要，并且我们通过定点诱变发现pkc依赖性NR2A磷酸化（Ser(1416)）是抑制α CaMKII结合和促进α CaMKII解离的关键机制（）。NR2A复杂。此外，我们发现，无论是用酚酯还是用mGluRs特异性激动剂反式-1-氨基-1,3-环戊二甲酸（t-ACPD）刺激海马切片中的PKC活性，都会降低α - CaMKII与NMDA受体复合物的结合。因此，我们的数据为理解突触后室中α - CaMKII和PKC通路之间直接串扰的分子基础提供了线索。
The N-methyl-D-aspartate (NMDA) receptor subunits NR2 possess extended intracellular C-terminal domains by which they can directly interact with a large number of postsynaptic density (PSD) proteins involved in synaptic clustering and signaling. We have previously shown that PSD-associated alpha -calmodulin kinase II (alpha CaMKII) binds with high affinity to the C-terminal domain of the NR2A subunit, Here, we show that residues 1412-1419 of the cytosolic tail of NR2A are critical for alpha CaMKII binding, and we identify, by site directed mutagenesis, PKC-dependent phosphorylation of NR2A(Ser(1416)) as a key mechanism in inhibiting alpha CaMKII-binding and promoting dissociation of alpha CaMKII(.)NR2A complex. In addition, we show that stimulation of PKC activity in hippocampal slices either with phorbol esters or with the mGluRs specific agonist trans-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD) decreases alpha CaMKII binding to NMDA receptor complex. Thus, our data provide clues on understanding the molecular basis of a direct cross-talk between alpha CaMKII and PKC pathways in the postsynaptic compartment.