Bouchut Anne, Chawla Aarti R, Jeffers Victoria, Hudmon Andy, Sullivan William J
Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, United States of America.
Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, United States of America.
PLoS One. 2015 Mar 18;10(3):e0117966. doi: 10.1371/journal.pone.0117966. eCollection 2015.
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.
赖氨酸乙酰化是一种可逆的翻译后修饰（PTM），几乎在所有细胞区室中的数千种蛋白质上都已检测到。这种广泛存在的PTM的作用尚未完全阐明，但它可以影响蛋白质的定位、相互作用、活性和稳定性。在这里，我们展示了对皮质星形胶质细胞中赖氨酸乙酰化的首次全蛋白质组学研究，皮质星形胶质细胞是神经胶质细胞的一种亚型，是血脑屏障的组成部分，也是神经元功能和可塑性的关键调节因子。我们在多个细胞区室中发现的304种蛋白质上鉴定出了529个赖氨酸乙酰化位点，这些蛋白质主要在RNA加工/转录、代谢、染色质生物学和翻译中发挥作用。我们在186种蛋白质上鉴定出的277个乙酰化赖氨酸在之前的任何其他细胞类型中均未被报道过。我们还绘制了感染脑寄生虫弓形虫的星形胶质细胞的乙酰化蛋白质组图谱。已经表明，弓形虫感染会调节宿主细胞基因表达，包括几个赖氨酸乙酰转移酶（KAT）和去乙酰化酶（KDAC）基因，这表明宿主的乙酰化蛋白质组可能在感染过程中也会发生改变。在感染弓形虫的星形胶质细胞中，我们鉴定出34种乙酰化水平相对于未感染星形胶质细胞增加>2倍的蛋白质，以及24种乙酰化水平<2倍的蛋白质。我们的研究记录了皮质星形胶质细胞的首张乙酰化蛋白质组图谱，发现了新的赖氨酸乙酰化位点，并证明弓形虫感染会导致乙酰化蛋白质组发生改变。
