Astrocyte-derived phosphatidic acid promotes dendritic branching.
Astrocyte-derived phosphatidic acid promotes dendritic branching.
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星形胶质细胞衍生的磷脂酸促进树突分支。
DOI：
10.1038/srep21096
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发表时间：
2016-02-17
影响因子：
4.6
通讯作者：
Yin DM
中科院分区：
文献类型：
--
作者：
Zhu YB;Gao W;Zhang Y;Jia F;Zhang HL;Liu YZ;Sun XF;Yin Y;Yin DM
星形胶质细胞在神经回路的形成和功能中起着关键作用。最近的研究揭示了星形胶质细胞分泌的和接触介导的信号，这些信号对神经突生长和突触形成至关重要。然而，星形胶质细胞调节树突状细胞分支的机制仍然难以捉摸。磷脂酶D1（PLD 1）催化磷脂酰胆碱（PC）水解生成磷脂酸（PA）和胆碱，参与神经突生长的调控。在这里，我们发现，敲低PLD 1选择性地在星形胶质细胞减少神经元-胶质细胞混合培养的神经元的树突状分支。进一步的研究表明，星形胶质细胞PLD 1通过分泌信号调节树突状细胞的分支。我们后来证明PA是星形胶质细胞PLD 1调节树枝状分支的关键介质。此外，PA本身足以促进神经元的树突状分支。最后，我们发现PA可以激活神经元中的蛋白激酶A（PKA），并通过PKA信号促进树突分支。总之，我们的研究结果表明，星形胶质细胞PLD 1和它的脂质产物PA是神经元树突分支的重要调节因子。这些结果可能为星形胶质细胞调节神经元树突生长的机制提供新的见解。
Astrocytes play critical roles in neural circuit formation and function. Recent studies have revealed several secreted and contact-mediated signals from astrocytes which are essential for neurite outgrowth and synapse formation. However, the mechanisms underlying the regulation of dendritic branching by astrocytes remain elusive. Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine (PC) to generate phosphatidic acid (PA) and choline, has been implicated in the regulation of neurite outgrowth. Here we showed that knockdown of PLD1 selectively in astrocytes reduced dendritic branching of neurons in neuron-glia mixed culture. Further studies from sandwich-like cocultures and astrocyte conditioned medium suggested that astrocyte PLD1 regulated dendritic branching through secreted signals. We later demonstrated that PA was the key mediator for astrocyte PLD1 to regulate dendritic branching. Moreover, PA itself was sufficient to promote dendritic branching of neurons. Lastly, we showed that PA could activate protein kinase A (PKA) in neurons and promote dendritic branching through PKA signaling. Taken together, our results demonstrate that astrocyte PLD1 and its lipid product PA are essential regulators of dendritic branching in neurons. These results may provide new insight into mechanisms underlying how astrocytes regulate dendrite growth of neurons.