Cellular phosphatidic acid sensor, α-synuclein N-terminal domain, detects endogenous phosphatidic acid in macrophagic phagosomes and neuronal growth cones
Cellular phosphatidic acid sensor, α-synuclein N-terminal domain, detects endogenous phosphatidic acid in macrophagic phagosomes and neuronal growth cones
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细胞磷脂酸传感器，α-突触核蛋白 N 末端结构域，检测巨噬细胞吞噬体和神经元生长锥中的内源磷脂酸
DOI：
10.1016/j.bbrep.2020.100769
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发表时间：
2020
影响因子：
2.7
通讯作者：
Sakane Fumio
中科院分区：
文献类型：
--
作者：
Yamada Haruka;Hoshino Fumi;Lu Qiang;Sakane Fumio
磷脂酸（PA）是最简单的磷脂，参与各种细胞事件的调节。最近，我们开发了一种新的PA传感器，α-synuclein的N-末端区域（α-Syn-N）。然而，α-Syn-N是否能感知生理产生的内源性PA仍不清楚。我们首先通过用谷氨酰胺残基替换所有11个赖氨酸残基来建立无活性PA传感器（α-Syn-N-KQ）作为阴性对照。使用共聚焦显微镜，我们接下来验证了α-Syn-N，而不是α-Syn-N-KQ，在已知PA富集的巨噬细胞吞噬体中检测到PA，进一步表明α-Syn-N可以用作细胞中可靠的PA传感器。最后，由于在神经元分化过程中产生的PA对神经突生长至关重要，我们使用α-Syn-N研究了PA的亚细胞分布。我们发现，α-Syn-N，而不是α-Syn-N-KQ，聚集在周边区域（靠近质膜）的神经生长锥。使用磷脂酶D（PLD）抑制剂的实验强烈表明，PA在周边地区的生长锥主要是由PLD。我们的研究结果提供了一个可靠的传感器内源性PA和新的见解PA在神经元分化过程中的分布。
Phosphatidic acid (PA) is the simplest phospholipid and is involved in the regulation of various cellular events. Recently, we developed a new PA sensor, the N-terminal region of α-synuclein (α-Syn-N). However, whether α-Syn-N can sense physiologically produced, endogenous PA remains unclear. We first established an inactive PA sensor (α-Syn-N-KQ) as a negative control by replacing all eleven lysine residues with glutamine residues. Using confocal microscopy, we next verified that α-Syn-N, but not α-Syn-N-KQ, detected PA in macrophagic phagosomes in which PA is known to be enriched, further indicating that α-Syn-N can be used as a reliable PA sensor in cells. Finally, because PA generated during neuronal differentiation is critical for neurite outgrowth, we investigated the subcellular distribution of PA using α-Syn-N. We found that α-Syn-N, but not α-Syn-N-KQ, accumulated at the peripheral regions (close to the plasma membrane) of neuronal growth cones. Experiments using a phospholipase D (PLD) inhibitor strongly suggested that PA in the peripheral regions of the growth cone was primarily produced by PLD. Our findings provide a reliable sensor of endogenous PA and novel insights into the distribution of PA during neuronal differentiation.
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1111/j.1748-1716.2011.02298.x
发表时间：
2012-02
期刊：
Acta physiologica (Oxford, England)
影响因子：
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作者：
Peng X;Frohman MA
通讯作者：
Frohman MA