Proteome-wide lysine acetylation in cortical astrocytes and alterations that occur during infection with brain parasite Toxoplasma gondii.
Proteome-wide lysine acetylation in cortical astrocytes and alterations that occur during infection with brain parasite Toxoplasma gondii.
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DOI：
10.1371/journal.pone.0117966
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Sullivan WJ Jr
中科院分区：
文献类型：
--
作者：
Bouchut A;Chawla AR;Jeffers V;Hudmon A;Sullivan WJ Jr
赖氨酸乙酰化是一种可逆的翻译后修饰（PTM），已在几乎所有细胞区室中的数千种蛋白质上检测到。这种广泛存在的PTM的作用尚未完全阐明，但可以影响蛋白质定位，相互作用，活性和稳定性。在这里，我们提出了第一个蛋白质组范围的调查，在皮质星形胶质细胞，神经胶质细胞的一个亚型，是血脑屏障的组成部分和神经元功能和可塑性的关键调节赖氨酸乙酰化。我们在多个细胞区室中发现的304种蛋白质中鉴定了529个赖氨酸乙酰化位点，这些蛋白质在RNA加工/转录、代谢、染色质生物学和翻译中发挥重要作用。我们在186个蛋白质上鉴定出的277个乙酰化赖氨酸以前在任何其他细胞类型中都没有报道过。我们还绘制了脑寄生虫弓形虫感染的星形胶质细胞的乙酰组。研究表明，T.弓形虫调节宿主细胞基因表达，包括几个赖氨酸乙酰转移酶（KAT）和脱乙酰酶（KDAC）基因，表明宿主乙酰组在感染期间也可能改变。在T.在刚第虫感染的星形胶质细胞中，我们鉴定了相对于未感染的星形胶质细胞，34种蛋白表现出乙酰化水平>2倍，24种蛋白表现出乙酰化水平<2倍。我们的研究记录了皮质星形胶质细胞的第一个乙酰组图谱，发现了新的赖氨酸乙酰化位点，并证明了T。弓形虫感染产生改变的乙酰组。
Lysine acetylation is a reversible post-translational modification (PTM) that has been detected on thousands of proteins in nearly all cellular compartments. The role of this widespread PTM has yet to be fully elucidated, but can impact protein localization, interactions, activity, and stability. Here we present the first proteome-wide survey of lysine acetylation in cortical astrocytes, a subtype of glia that is a component of the blood-brain barrier and a key regulator of neuronal function and plasticity. We identified 529 lysine acetylation sites across 304 proteins found in multiple cellular compartments that largely function in RNA processing/transcription, metabolism, chromatin biology, and translation. Two hundred and seventy-seven of the acetylated lysines we identified on 186 proteins have not been reported previously in any other cell type. We also mapped an acetylome of astrocytes infected with the brain parasite, Toxoplasma gondii. It has been shown that infection with T. gondii modulates host cell gene expression, including several lysine acetyltransferase (KAT) and deacetylase (KDAC) genes, suggesting that the host acetylome may also be altered during infection. In the T. gondii-infected astrocytes, we identified 34 proteins exhibiting a level of acetylation >2-fold and 24 with a level of acetylation <2-fold relative to uninfected astrocytes. Our study documents the first acetylome map for cortical astrocytes, uncovers novel lysine acetylation sites, and demonstrates that T. gondii infection produces an altered acetylome.
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影响因子：
56.9
作者：
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通讯作者：
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