Distinct Roles of Protein Phosphatase 1 Bound on Neurabin and Spinophilin and Its Regulation in AMPA Receptor Trafficking and LTD Induction.
Distinct Roles of Protein Phosphatase 1 Bound on Neurabin and Spinophilin and Its Regulation in AMPA Receptor Trafficking and LTD Induction.
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DOI：
10.1007/s12035-018-0886-2
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发表时间：
2018-09
影响因子：
5.1
通讯作者：
Xia H
中科院分区：
文献类型：
--
作者：
Gao J;Hu XD;Yang H;Xia H
蛋白磷酸酶-1（PP 1）部分通过影响长时程增强（LTP）和抑郁（LTD）的诱导阈值来抑制学习和记忆的形成。LTD诱导需要PP 1的酶活性及其与突触棘的适当锚定。我们以前已经表明，neurabin，一个主要的突触支架蛋白，目标PP 1突触LTD诱导。在这里，我们表明，亲棘素，neurabin和另一个主要的突触PP 1锚定蛋白的密切同源物，不发挥LTD诱导的作用，这表明，neurabin在LTD诱导PP 1的纳米结构域靶向中起着特殊的作用。我们发现，蛋白激酶A可以显着削弱神经元中的神经肽-PP 1的相互作用，通过磷酸化的神经肽在丝氨酸461，磷酸化位点附近的PP 1结合基序，是不保守的spinophilin。最后，我们发现神经肽突变（S461 E），模拟磷酸化，阻断AMPA受体的内吞作用和LTD诱导。结果表明，突触棘内PP 1的纳米结构域靶向及其在LTD诱导中的调节至关重要。
Protein Phosphatase-1 (PP1) constrains learning and memory formation in part through its effects on the induction threshold of long term potentiation (LTP) and depression (LTD). LTD induction requires both the enzymatic activity of PP1 and its proper anchoring to synaptic spines. We have shown previously that neurabin, a major synaptic scaffolding protein, targets PP1 to synapses for LTD induction. Here, we show that spinophilin, a close homologue of neurabin and another major synaptic PP1 anchoring protein, does not play a role in LTD induction, which suggests that neurabin plays a privileged role in nanodomain targeting of PP1 in LTD induction. We found that protein kinase A can significantly weaken the neurabin-PP1 interaction in neurons via phosphorylation of neurabin at serine 461, a phosphorylation site adjacent to the PP1 binding motif that is not conserved in spinophilin. Finally, we found that a neurabin mutation (S461E), which mimics phosphorylation, blocked AMPA receptor endocytosis and LTD induction. The results indicate the critical importance of nanodomain targeting of PP1 within synaptic spines and its regulation in LTD induction.
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DOI：
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发表时间：
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影响因子：
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作者：
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DOI：
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发表时间：
2000-08-01
影响因子：
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