Siglecs are cell surface receptors whose functions are tied to the binding of their sialoglycan ligands. Recently, we developed an optimized liposome formulation and used it to investigate the binding of human Siglecs (hSiglec) against a panel of gangliosides. Animal models, more specifically murine models, are used to understand human biology; however, species-specific differences can complicate the interpretation of the results. Herein, we used our optimized liposome formulation to dissect the interactions between murine Siglecs (mSiglecs) and gangliosides to assess the appropriateness of mSiglecs as a proxy to better understand the biological roles of hSiglec–ganglioside interactions. Using our optimized liposome formulation, we found that ganglioside binding is generally conserved between mice and humans with mSiglec-1, -E, -F, and -15 binding multiple gangliosides like their human counterparts. However, in contrast to the hSiglecs, we observed little to no binding between the mSiglecs and ganglioside GM1a. Detailed analysis of mSiglec-1 interacting with GM1a and its structural isomer, GM1b, suggests that mSiglec-1 preferentially binds α2-3–linked sialic acids presented from the terminal galactose residue. The ability of mSiglecs to interact or not interact with gangliosides, particularly GM1a, has implications for using mice to study neurodegenerative diseases, infections, and cancer, where interactions between Siglecs and glycolipids have been proposed to modulate these human diseases.

中文翻译：

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剖析小鼠 Siglecs 与神经节苷脂相互作用的能力


Siglec 是细胞表面受体，其功能与其唾液聚糖配体的结合有关。最近，我们开发了一种优化的脂质体配方，并用它来研究人 Siglecs (hSiglec) 与一组神经节苷脂的结合。动物模型，更具体地说是小鼠模型，用于理解人类生物学；然而，物种特异性差异可能会使结果的解释复杂化。在此，我们使用优化的脂质体配方来剖析小鼠 Siglecs (mSiglecs) 和神经节苷脂之间的相互作用，以评估 mSiglecs 作为代理的适当性，以更好地了解 hSiglec-神经节苷脂相互作用的生物学作用。使用我们优化的脂质体配方，我们发现神经节苷脂结合在小鼠和人类之间通常是保守的，mSiglec-1、-E、-F 和 -15 与人类对应物一样结合多种神经节苷脂。然而，与 hSiglecs 相比，我们观察到 mSiglecs 和神经节苷脂 GM1a 之间几乎没有结合。对 mSiglec-1 与 GM1a 及其结构异构体 GM1b 相互作用的详细分析表明，mSiglec-1 优先结合来自末端半乳糖残基的 α2-3 连接唾液酸。 mSiglecs 与神经节苷脂（特别是 GM1a）相互作用或不相互作用的能力对于使用小鼠研究神经退行性疾病、感染和癌症具有重要意义，其中 Siglecs 和糖脂之间的相互作用已被提议来调节这些人类疾病。