Actin-associated neurabin-protein phosphatase-1 complex regulates hippocampal plasticity
Actin-associated neurabin-protein phosphatase-1 complex regulates hippocampal plasticity
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DOI：
10.1111/j.1471-4159.2006.04070.x
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发表时间：
2006-09-01
影响因子：
4.7
通讯作者：
Xia, Houhui
中科院分区：
文献类型：
--
作者：
Hu, Xiao Dong;Huang, Qing;Xia, Houhui
蛋白磷酸酶-1 (PP1) 与大鼠海马 CA1 神经元长时程增强 (LTP) 和抑制 (LTD) 的控制有关。 PP1 催化亚基与多个突触后调节亚基相关，但控制大鼠海马 LTP 和 LTD 的 PP1 复合物仍未确定。神经元特异性肌动蛋白结合蛋白 Neurabin-I 在树突棘中富集，并将 PP1 与富含肌动蛋白的突触后密度连接起来，以调节树突棘的形态和成熟。本研究利用辛德比斯病毒介导的大鼠海马切片器官型培养物中野生型和突变型神经蛋白-I 多肽的表达来研究它们在突触可塑性中的作用。虽然野生型 Neurabin-I 不会引起基础突触传递的变化，但它增强了 CA1 锥体神经元中的 LTD 并抑制了 LTP。相比之下，突变的神经蛋白，特别是那些不能结合 PP1 或 F-肌动蛋白的神经蛋白，在切片培养物中减少了基础突触传递，减弱了 LTD 并增加了 LTP。生化和细胞生物学分析表明，通过错误定位突触 PP1，突变型神经蛋白损害了内源性神经蛋白-PP1 复合物的功能并调节了 LTP 和 LTD。总之，这些研究提供了第一个生化和生理学证据，表明突触后肌动蛋白结合的神经蛋白-I-PP1 复合物调节突触传递和海马可塑性的双向变化。
Protein phosphatase-1 (PP1) has been implicated in the control of long-term potentiation (LTP) and depression (LTD) in rat hippocampal CA1 neurons. PP1 catalytic subunits associate with multiple postsynaptic regulatory subunits, but the PP1 complexes that control hippocampal LTP and LTD in the rat hippocampus remain unidentified. The neuron-specific actin-binding protein, neurabin-I, is enriched in dendritic spines, and tethers PP1 to actin-rich postsynaptic density to regulate morphology and maturation of spines. The present studies utilized Sindbis virus-mediated expression of wild-type and mutant neurabin-I polypeptides in organotypic cultures of rat hippocampal slices to investigate their role in synaptic plasticity. While wild-type neurabin-I elicited no change in basal synaptic transmission, it enhanced LTD and inhibited LTP in CA1 pyramidal neurons. By comparison, mutant neurabins, specifically those unable to bind PP1 or F-actin, decreased basal synaptic transmission, attenuated LTD and increased LTP in slice cultures. Biochemical and cell biological analyses suggested that, by mislocalizing synaptic PP1, the mutant neurabins impaired the functions of endogenous neurabin-PP1 complexes and modulated LTP and LTD. Together, these studies provided the first biochemical and physiological evidence that a postsynaptic actin-bound neurabin-I-PP1 complex regulates synaptic transmission and bidirectional changes in hippocampal plasticity.