The diacylglycerol-binding protein α1-chimaerin regulates dendritic morphology
The diacylglycerol-binding protein α1-chimaerin regulates dendritic morphology
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DOI：
10.1073/pnas.0510655103
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发表时间：
2006-02-07
影响因子：
11.1
通讯作者：
Scheiffele, P
中科院分区：
文献类型：
--
作者：
Buttery, P;Beg, AA;Scheiffele, P
神经元树突的形态和功能分化是通过转录程序和细胞间信号传导控制的。突触活动被认为在树突乔木的成熟中发挥重要作用，但耦合神经元活动和树突形态变化的信号通路尚不清楚。我们探索了 α1-chimaerin 的功能，α1-chimaerin 是一种神经元二酰基甘油结合蛋白，具有 Rho GTP 酶激活蛋白结构域，可灭活 Rac1。我们发现，刺激磷脂酶 C β 偶联细胞表面受体会将 α1-嵌合蛋白募集到培养的海马神经元的质膜上。我们进一步表明，α1-嵌合蛋白水平受突触活性控制，并且α1-嵌合蛋白表达增加会导致树突棘和分支的修剪。这种修剪活性需要 α1-嵌合蛋白的二酰基甘油结合和 Rac GTP 酶激活蛋白活性。 α1-嵌合蛋白表达的抑制导致树突轴和棘头的突起生长增加。我们的数据表明，α1-嵌合蛋白是一种活性调节的 Rho GTP 酶调节剂，由磷脂酶 C β 偶联细胞表面受体激活，有助于修剪树突乔木。
The morphological and functional differentiation of neuronal dendrites is controlled through transcriptional programs and cell-cell signaling. Synaptic activity is thought to play an important role in the maturation of dendritic arbors, but the signaling pathways that couple neuronal activity and morphological changes in dendrites are not well understood. We explored the function of alpha 1-chimaerin, a neuronal diacylglycerol-binding protein with a Rho GTPase-activating protein domain that inactivates Rac1. We find that stimulation of phospholipase C beta-coupled cell surface receptors recruits alpha 1-chimaerin to the plasma membrane of cultured hippocampal neurons. We further show that alpha 1-chimaerin protein levels are controlled by synaptic activity and that increased alpha 1-chimaerin expression results in the pruning of dendritic spines and branches. This pruning activity requires both the diacylglycerol-binding and Rac GTPase-activating protein activity of alpha 1-chimaerin. Suppression of alpha 1-chimaerin expression resulted in increased process growth from the dendritic shaft and from spine heads. Our data suggest that alpha 1-chimaerin is an activity-regulated Rho GTPase regulator that is activated by phospholipase C beta-coupled cell surface receptors and contributes to pruning of dendritic arbors.