Complexity and Diversity of the Mammalian Sialome Revealed by Nidovirus Virolectins.
Complexity and Diversity of the Mammalian Sialome Revealed by Nidovirus Virolectins.
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DOI：
10.1016/j.celrep.2015.05.044
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发表时间：
2015-06-30
期刊：
影响因子：
8.8
通讯作者：
de Groot RJ
中科院分区：
文献类型：
--
作者：
Langereis MA;Bakkers MJ;Deng L;Padler-Karavani V;Vervoort SJ;Hulswit RJ;van Vliet AL;Gerwig GJ;de Poot SA;Boot W;van Ederen AM;Heesters BA;van der Loos CM;van Kuppeveld FJ;Yu H;Huizinga EG;Chen X;Varki A;Kamerling JP;de Groot RJ
唾液酸（Sias），9碳骨架糖，是最复杂和最多功能的生命分子之一。作为蛋白质和脂质上聚糖的末端残基，Sias是细胞和微生物凝集素的糖表位的关键元件，因此在细胞识别和信号传导事件中充当重要的分子标签。它们在这种相互作用中的功能可以通过合成后修饰来调节，其中最常见的是差异Sia-O-乙酰化（O-Ac-Sias）。O-Ac-Sias的生物学仍然大部分未被探索，主要是因为与其特异性原位检测相关的限制。在这里，我们表明，双功能血凝素酯酶包膜蛋白的巢状病毒区分各种密切相关的O-Ac-Sias。通过使用可溶性形式的血凝素-酯酶作为凝集素和唾液酸-O-乙酰酯酶，我们证明了不同的O-Ac-唾液酸聚糖群体在器官，组织和细胞特异性方式的差异表达。我们的研究结果表明，程序化Sia-O-乙酰化/去-O-乙酰化可能对细胞发育，稳态和/或功能的关键方面至关重要。病毒凝集素原位检测和区分密切相关的O-Ac-Sias O-Ac-唾液酸聚糖在自然界中存在的多样性迄今为止尚未被认识到O-Ac-Sias以物种特异性、组织特异性和细胞特异性的方式差异表达。O-Ac-Sias在体内和体外的表达存在广泛的细胞间差异。合成后修饰的唾液酸在生物分子识别事件中充当关键标签，无论是健康还是疾病。Langereis等人介绍了基于巢状病毒凝集素和酶原位检测不同O-乙酰化唾液酸种类的方法，并通过探索哺乳动物细胞和组织中唾液酸聚糖的分布来证明其适用性。
Sialic acids (Sias), 9-carbon-backbone sugars, are among the most complex and versatile molecules of life. As terminal residues of glycans on proteins and lipids, Sias are key elements of glycotopes of both cellular and microbial lectins and thus act as important molecular tags in cell recognition and signaling events. Their functions in such interactions can be regulated by post-synthetic modifications, the most common of which is differential Sia-O-acetylation (O-Ac-Sias). The biology of O-Ac-Sias remains mostly unexplored, largely because of limitations associated with their specific in situ detection. Here, we show that dual-function hemagglutinin-esterase envelope proteins of nidoviruses distinguish between a variety of closely related O-Ac-Sias. By using soluble forms of hemagglutinin-esterases as lectins and sialate-O-acetylesterases, we demonstrate differential expression of distinct O-Ac-sialoglycan populations in an organ-, tissue- and cell-specific fashion. Our findings indicate that programmed Sia-O-acetylation/de-O-acetylation may be critical to key aspects of cell development, homeostasis, and/or function. Virolectins detect and distinguish between closely related O-Ac-Sias in situ O-Ac-sialoglycans occur in nature in a diversity not appreciated so far O-Ac-Sias are differentially expressed in a species-, tissue-, and cell-specific fashion There is extensive cell-to-cell variability in O-Ac-Sia expression in vivo and in vitro Postsynthetically modified sialic acids serve as critical tags in biomolecular recognition events, both in health and disease. Langereis et al. introduce methodology, based on nidovirus lectins and enzymes, for in situ detection of distinct O-acetylated sialic acid species and demonstrate its applicability by exploring sialoglycan distribution in mammalian cells and tissues.