Photoproximity Labeling of Sialylated Glycoproteins (GlycoMap) Reveals Sialylation-Dependent Regulation of Ion Transport,Journal of the American Chemical Society

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Photoproximity Labeling of Sialylated Glycoproteins (GlycoMap) Reveals Sialylation-Dependent Regulation of Ion Transport
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2022-12-16 , DOI: 10.1021/jacs.2c11094
Claudio F Meyer _{1,

2} , Ciaran P Seath _{1,

2} , Steve D Knutson _{1,

2} , Wenyun Lu _{2,

3} , Joshua D Rabinowitz _{2,

3,

4} , David W C MacMillan _{1,

2}

Affiliation

Sialylation, the addition of sialic acid to glycans, is a crucial post-translational modification of proteins, contributing to neurodevelopment, oncogenesis, and immune response. In cancer, sialylation is dramatically upregulated. Yet, the functional biochemical consequences of sialylation remain mysterious. Here, we establish a μMap proximity labeling platform that utilizes metabolically inserted azidosialic acid to introduce iridium-based photocatalysts on sialylated cell–surface glycoproteins as a means to profile local microenvironments across the sialylated proteome. In comparative experiments between primary cervical cells and a cancerous cell line (HeLa), we identify key differences in both the global sialome and proximal proteins, including solute carrier proteins that regulate metabolite and ion transport. In particular, we show that cell–surface interactions between receptors trafficking ethanolamine and zinc are sialylation-dependent and impact intracellular metabolite levels. These results establish a μMap method for interrogating proteoglycan function and support a role for sialylated glycoproteins in regulating cell–surface transporters.

中文翻译：

唾液酸化糖蛋白的光邻近标记 (GlycoMap) 揭示了离子传输的唾液酸化依赖性调节

唾液酸化，即在聚糖上添加唾液酸，是蛋白质的重要翻译后修饰，有助于神经发育、肿瘤发生和免疫反应。在癌症中，唾液酸化显着上调。然而，唾液酸化的功能性生化后果仍然是个谜。在这里，我们建立了一个 μMap 邻近标记平台，利用代谢插入的叠氮唾液酸在唾液酸化细胞表面糖蛋白上引入基于铱的光催化剂，作为分析唾液酸化蛋白质组局部微环境的手段。在原代宫颈细胞和癌细胞系（HeLa）之间的比较实验中，我们确定了整体硅质体和近端蛋白（包括调节代谢物和离子运输的溶质载体蛋白）的关键差异。特别是，我们发现运输乙醇胺和锌的受体之间的细胞表面相互作用是唾液酸化依赖性的，并影响细胞内代谢物水平。这些结果建立了一种用于检测蛋白聚糖功能的 μMap 方法，并支持唾液酸化糖蛋白在调节细胞表面转运蛋白中的作用。

更新日期：2022-12-16

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