Involvement of diacylglycerol kinase B in the spine formation at distal dendrites of striatal medium spiny neurons.
Involvement of diacylglycerol kinase B in the spine formation at distal dendrites of striatal medium spiny neurons.
复制标题
二酰甘油激酶 B 参与纹状体中型多棘神经元远端树突的棘形成。
DOI：
10.1016/j.brainres.2014.11.012
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Goto K
中科院分区：
文献类型：
--
作者：
Hozumi Y;Kakefuda K;Yamasaki M;Watanabe M;Hara H;Goto K
棘的形成是神经元可塑性适应环境变化的一个重要特征，它受到膜信号转导等复杂机制的调控。甘油二酯激酶（DGK）家族参与膜脂质代谢，催化脂质第二信使甘油二酯（DG）的磷酸化。在DGK中，DGKβ的特征在于在特定的脑区域：纹状体中主要表达。我们先前证明DGKβ选择性地表达于中型棘神经元（MSNs），并且在与兴奋性终末接触的树突棘上的突触周膜中高度富集。此外，DGKβ以活性依赖性方式通过基于肌动蛋白的重塑调节棘发生。然而，棘发生调控的详细机制及其功能意义仍不清楚。为了解决这些问题，我们进行了Golgi-Cox染色以检查DGKβ敲除（KO）小鼠纹状体中MSN的形态学方面。结果显示，DGKβ-KO小鼠的MSNs在远端树突处的树突棘密度低于野生型小鼠。我们还寻找与DGKβ相互作用的蛋白质靶点，并将GluA 2 AMPA受体亚基鉴定为新型DGKβ结合伴侣。此外，DGKβ缺陷的脑表现出TARP γ-8的显著减少，TARP γ-8代表跨膜AMPA受体调节蛋白。这些结果表明，DGKβ调节MSNs远端树突棘的形成。
Spine formation, a salient feature underlying neuronal plasticity to adapt to a changing environment, is regulated by complex machinery involving membrane signal transduction. The diacylglycerol kinase (DGK) family, which is involved in membrane lipid metabolism, catalyzes the phosphorylation of a lipid second messenger, diacylglycerol (DG). Of the DGKs, DGKβ is characterized by predominant expression in a specific brain region: the striatum. We previously demonstrated that DGKβ is expressed selectively in medium spiny neurons (MSNs) and that it is highly enriched in the perisynaptic membrane on dendritic spines contacted with excitatory terminals. Moreover, DGKβ regulates spinogenesis through actin-based remodeling in an activity-dependent manner. However, the detailed mechanisms of spinogenesis regulation and its functional significance remain unclear. To address these issues, we performed Golgi–Cox staining to examine morphological aspects of MSNs in the striatum of DGKβ-knockout (KO) mice. Results show that striatal MSNs of DGKβ-KO mice exhibited lower dendritic spine density at distal dendrites than wild-type mice did. We also sought protein targets that interact with DGKβ and identified the GluA2 AMPA receptor subunit as a novel DGKβ binding partner. In addition, DGKβ-deficient brain exhibits significant reduction of TARP γ-8, which represents a transmembrane AMPA receptor regulatory protein. These findings suggest that DGKβ regulates the spine formation at distal dendrites in MSNs.