Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110166, China; The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang 110866, China.
Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110166, China; The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang 110866, China.
Genomics Proteomics Bioinformatics. 2023 Dec;21(6):1163-1181. doi: 10.1016/j.gpb.2022.09.010. Epub 2022 Oct 7.
The biology of Toxoplasma gondii, the causative pathogen of one of the most widespread parasitic diseases (toxoplasmosis), remains poorly understood. Lactate, which is derived from glucose metabolism, is not only an energy source in a variety of organisms, including T. gondii, but also a regulatory molecule that participates in gene activation and protein function. Lysine lactylation (Kla) is a type of post-translational modifications (PTMs) that has been recently associated with chromatin remodeling; however, Kla of histone and non-histone proteins has not yet been studied in T. gondii. To examine the prevalence and function of lactylation in T. gondii parasites, we mapped the lactylome of proliferating tachyzoite cells and identified 1964 Kla sites on 955 proteins in the T. gondii RH strain. Lactylated proteins were distributed in multiple subcellular compartments and were closely related to a wide variety of biological processes, including mRNA splicing, glycolysis, aminoacyl-tRNA biosynthesis, RNA transport, and many signaling pathways. We also performed a chromatin immunoprecipitation sequencing (ChIP-seq) analysis using a lactylation-specific antibody and found that the histones H4K12la and H3K14la were enriched in the promoter and exon regions of T. gondii associated with microtubule-based movement and cell invasion. We further confirmed the delactylase activity of histone deacetylases TgHDAC2-4, and found that treatment with anti-histone acetyltransferase (TgMYST-A) antibodies profoundly reduced protein lactylation in T. gondii. This study offers the first dataset of the global lactylation proteome and provides a basis for further dissecting the functional biology of T. gondii.
刚地弓形虫的生物学，一种最广泛的寄生虫病（弓形体病）的病原体，仍然知之甚少。乳酸盐，来自葡萄糖代谢，不仅是包括刚地弓形虫在内的多种生物的能量来源，而且还是一种调节分子，参与基因激活和蛋白质功能。赖氨酸乳酸化（Kla）是一种最近与染色质重塑相关的翻译后修饰（PTMs）类型；然而，刚地弓形虫中的组蛋白和非组蛋白蛋白质的 Kla 尚未被研究。为了研究乳酸化在刚地弓形虫寄生虫中的普遍性和功能，我们绘制了增殖速殖子细胞的乳酸组图谱，并在 RH 株的刚地弓形虫中鉴定了 955 种蛋白质上的 1964 个 Kla 位点。乳酸化蛋白分布在多个亚细胞区室中，与广泛的生物学过程密切相关，包括 mRNA 剪接、糖酵解、氨酰-tRNA 生物合成、RNA 转运和许多信号通路。我们还使用乳酸化特异性抗体进行了染色质免疫沉淀测序（ChIP-seq）分析，发现组蛋白 H4K12la 和 H3K14la 在与微管相关的运动和细胞入侵相关的刚地弓形虫的启动子和外显子区域中富集。我们进一步证实了组蛋白去乙酰化酶 TgHDAC2-4 的脱乙酰酶活性，并发现用抗组蛋白乙酰转移酶（TgMYST-A）抗体处理可显著降低刚地弓形虫中的蛋白质乳酸化。这项研究提供了全球乳酸化蛋白质组的第一个数据集，并为进一步剖析刚地弓形虫的功能生物学提供了基础。
