The Rac-GAP alpha2-chimaerin regulates hippocampal dendrite and spine morphogenesis.
The Rac-GAP alpha2-chimaerin regulates hippocampal dendrite and spine morphogenesis.
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DOI：
10.1016/j.mcn.2016.06.002
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Beg AA
中科院分区：
文献类型：
--
作者：
Valdez CM;Murphy GG;Beg AA
树突棘是精细的神经元过程，其中空间受限的输入可以在一个棘中诱导活动依赖性变化，而使相邻的棘未被修改。形态学上的脊柱可塑性对于突触传递至关重要，并且被认为是学习和记忆等过程的基础。值得注意的是，树突棘稳定性和形态学缺陷是在几种神经发育和神经精神疾病中发现的常见致病特征。棘的重塑依赖于调节基本细胞骨架的蛋白质，所述细胞骨架主要由丝状（F）-肌动蛋白组成。Rho-GTCRac 1是F-肌动蛋白的主要调节因子，对树突和棘的发育和可塑性至关重要。然而，调控Rac 1依赖的棘和突触通路的关键分子和机制还没有很好地理解。我们已经鉴定了Rac 1-GT β激活蛋白，α2-chimaerin，作为海马神经元中Rac 1的关键负调节因子。α2-chimaerin的缺失显著增加了活性Rac 1的水平，并诱导异常多态性树突棘的形成。此外，α2-嵌合蛋白信号传导的中断简化了树突乔木的复杂性，并增加了出现多神经支配的树突棘的存在。我们的数据表明，α2-chimaerin作为一个“刹车”，以限制Rac 1依赖的信号，以确保响应网络活动的棘的成熟形态得以维持。
Dendritic spines are fine neuronal processes where spatially restricted input can induce activity-dependent changes in one spine, while leaving neighboring spines unmodified. Morphological spine plasticity is critical for synaptic transmission and is thought to underlie processes like learning and memory. Significantly, defects in dendritic spine stability and morphology are common pathogenic features found in several neurodevelopmental and neuropsychiatric disorders. The remodeling of spines relies on proteins that modulate the underlying cytoskeleton, which is primarily composed of filamentous (F)-actin. The Rho-GTPase Rac1 is a major regulator of F-actin and is essential for the development and plasticity of dendrites and spines. However, the key molecules and mechanisms that regulate Rac1-dependent pathways at spines and synapses are not well understood. We have identified the Rac1-GTPase activating protein, α2-chimaerin, as a critical negative regulator of Rac1 in hippocampal neurons. The loss of α2-chimaerin significantly increases the levels of active Rac1 and induces the formation of aberrant polymorphic dendritic spines. Further, disruption of α2-chimaerin signaling simplifies dendritic arbor complexity and increases the presence of dendritic spines that appear poly-innervated. Our data suggests that α2-chimaerin serves as a “brake” to constrain Rac1-dependent signaling to ensure that the mature morphology of spines is maintained in response to network activity.
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影响因子：
64.5
作者：
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通讯作者：
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25
作者：
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DOI：
10.1073/pnas.0510655103
发表时间：
2006-02-07
影响因子：
11.1
作者：
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通讯作者：
Scheiffele, P
DOI：
10.1073/pnas.0904636106
发表时间：
2009-08-04
影响因子：
11.1
作者：
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通讯作者：
Penzes, Peter