Translocation of autophosphorylated calcium/calmodulin-dependent protein kinase II to the postsynaptic density
Translocation of autophosphorylated calcium/calmodulin-dependent protein kinase II to the postsynaptic density
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DOI：
10.1074/jbc.272.21.13467
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发表时间：
1997-05-23
影响因子：
4.8
通讯作者：
Colbran, RJ
中科院分区：
文献类型：
--
作者：
Strack, S;Choi, S;Colbran, RJ
钙/钙调蛋白依赖性蛋白激酶 II (CaMKII) 经历钙依赖性自磷酸化，产生钙独立形式，可作为记忆的分子底物。在这里，我们表明，钙独立的 CaMKII 特异性结合分离的突触后密度 (PSD)，导致许多 PSD 蛋白的磷酸化增强，包括 α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸 (AMPA) 型谷氨酸受体。此外，与 PSD 的结合将 CaMKII 从蛋白磷酸酶 2A 的底物变为蛋白磷酸酶 I 底物。在诱导 CaMKII 自磷酸化和一种长期增强形式的治疗后，海马切片中发生 CaMKII 向 PSD 的易位。因此，突触激活导致 PSD 中自磷酸化、激活的 CaMKII 积累。这增加了底物磷酸化并影响蛋白磷酸酶对激酶的调节，这可能有助于增强突触强度。
Calcium/calmodulin-dependent protein kinase II (CaMKII) undergoes calcium-dependent autophosphorylation, generating a calcium-independent form that may serve as a molecular substrate for memory. Here we show that calcium-independent CaMKII specifically binds to isolated postsynaptic densities (PSDs), leading to enhanced phosphorylation of many PSD proteins including the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-type glutamate receptor. Furthermore, binding to PSDs changes CaMKII hom a substrate for protein phosphatase 2A to a protein phosphatase I substrate. Translocation of CaMKII to PSDs occurs in hippocampal slices following treatments that induce CaMKII autophosphorylation and a form of long term potentiation. Thus, synaptic activation leads to accumulation of autophosphorylated, activated CaMKII in the PSD. This increases substrate phosphorylation and affects regulation of the kinase by protein phosphatases, which may contribute to enhancement of synaptic strength.