Fukunaga K, Muller D, Ohmitsu M, Bakó E, DePaoli-Roach A A, Miyamoto E
Department of Pharmacology, Kumamoto University School of Medicine, Japan.
J Neurochem. 2000 Feb;74(2):807-17. doi: 10.1046/j.1471-4159.2000.740807.x.
Using autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) as substrate, we now find that long-term potentian (LTP) induction and maintenance are also associated with a significant decrease in calyculin A-sensitive protein phosphatase (protein phosphatase 2A) activity, without changes in Mg2+-dependent protein phosphatase (protein phosphatase 2C) activity. This decrease in protein phosphatase 2A activity was prevented when LTP induction was inhibited by treatment with calmidazolium or D-2-amino-5-phosphonopentanoic acid. In addition, the application of high-frequency stimulation to 32P-labeled hippocampal slices resulted in increases in the phosphorylation of a 55-kDa protein immunoprecipitated with anti-phosphatase 2A antibodies. Use of a specific antibody revealed that the 55-kDa protein is the B'alpha subunit of protein phosphatase 2A. Following purification of brain protein phosphatase 2A, the B'alpha subunit was phosphorylated by CaM kinase II, an event that led to the reduction of protein phosphatase 2A activity. These results suggest that the decreased activity in protein phosphatase 2A following LTP induction contributes to the maintenance of constitutively active CaM kinase II and to the long-lasting increase in phosphorylation of synaptic components implicated in LTP.
以自身磷酸化的钙/钙调蛋白依赖性蛋白激酶II（CaM激酶II）为底物，我们现在发现，长时程增强（LTP）的诱导和维持还与钙调神经磷酸酶A敏感蛋白磷酸酶（蛋白磷酸酶2A）活性的显著降低有关，而镁离子依赖性蛋白磷酸酶（蛋白磷酸酶2C）的活性没有变化。当用氯氮卓或D-2-氨基-5-磷酸戊酸处理抑制LTP诱导时，蛋白磷酸酶2A活性的这种降低被阻止。此外，对32P标记的海马切片施加高频刺激导致用抗磷酸酶2A抗体免疫沉淀的55 kDa蛋白的磷酸化增加。使用特异性抗体显示，55 kDa蛋白是蛋白磷酸酶2A的B'α亚基。纯化脑蛋白磷酸酶2A后，B'α亚基被CaM激酶II磷酸化，这一事件导致蛋白磷酸酶2A活性降低。这些结果表明，LTP诱导后蛋白磷酸酶2A活性的降低有助于维持组成型活性CaM激酶II，并有助于LTP中涉及的突触成分磷酸化的持久增加。
