Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity.
Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity.
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DOI：
10.1038/nature19784
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发表时间：
2016-10-06
期刊：
影响因子：
64.8
通讯作者：
Yasuda R
中科院分区：
文献类型：
--
作者：
Hedrick NG;Harward SC;Hall CE;Murakoshi H;McNamara JO;Yasuda R
Rho GT3蛋白Rac1、RhoA和Cdc42在调节树突棘中的肌动蛋白细胞骨架中具有核心作用，从而对棘的结构和功能可塑性以及最终的学习和记忆施加控制。虽然以前的工作已经表明，这些GTP酶的精确时空协调是至关重要的某些形式的细胞形态发生，这种协调的性质在结构脊柱可塑性尚不清楚。在这里，我们描述了一个三分子模型的结构长时程增强（sLTP）的小鼠树突棘，牵连本地化，一致的激活Rac1，RhoA和Cdc42作为一个因果信号sLTP。该模型假定，完整的三重信号重叠的棘赋予sLTP，但部分重叠的结构可塑性的引物棘。通过监测这些GTP酶在sLTP过程中的时空激活模式，我们发现这种时空信号互补同时解释了可塑性的三个整体特征：脑源性神经营养因子（BDNF）对可塑性的促进作用，其突触后来源激活Cdc42和Rac 1，但不激活RhoA;和输入特异性，这是由脊椎限制Cdc42活动。因此，我们提出了一种形式的生化计算树突涉及的控制互补的三个分子，同时确保信号的特异性和启动系统的可塑性。
The Rho GTPase proteins Rac1, RhoA and Cdc42 have a central role in regulating the actin cytoskeleton in dendritic spines, thereby exerting control over the structural and functional plasticity of spines and, ultimately, learning and memory. Although previous work has shown that precise spatiotemporal coordination of these GTPases is crucial for some forms of cell morphogenesis, the nature of such coordination during structural spine plasticity is unclear. Here we describe a three-molecule model of structural long-term potentiation (sLTP) of murine dendritic spines, implicating the localized, coincident activation of Rac1, RhoA and Cdc42 as a causal signal of sLTP. This model posits that complete tripartite signal overlap in spines confers sLTP, but that partial overlap primes spines for structural plasticity. By monitoring the spatiotemporal activation patterns of these GTPases during sLTP, we find that such spatiotemporal signal complementation simultaneously explains three integral features of plasticity: the facilitation of plasticity by brain-derived neurotrophic factor (BDNF), the postsynaptic source of which activates Cdc42 and Rac1, but not RhoA; heterosynaptic facilitation of sLTP, which is conveyed by diffusive Rac1 and RhoA activity; and input specificity, which is afforded by spine-restricted Cdc42 activity. Thus, we present a form of biochemical computation in dendrites involving the controlled complementation of three molecules that simultaneously ensures signal specificity and primes the system for plasticity.