Abstract：
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.
摘要：
Siglecs是细胞表面受体,其功能与其唾液酸聚糖配体的结合有关。最近,我们开发了一种优化的脂质体制剂，并将其用于研究人Siglecs（hSiglec）与一组神经节苷脂的结合。动物模型,更具体地说是鼠类模型，用来理解人类生物学，然而,物种特异性差异会使结果的解释复杂化。在这里，我们使用我们优化的脂质体配方来剖析鼠Siglecs(mSiglecs)和神经节苷脂之间的相互作用,以评估mSiglecs作为替代的适当性,从而更好地理解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，具有mSiglec-1，-E，-F,和-15结合多个神经节苷脂，就像它们的人类对应物一样。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。详细分析mSiglec-1与GM1a及其结构异构体的相互作用，GM1b,提示mSiglec-1优先结合从末端半乳糖残基呈现的α2-3连接的唾液酸。mSiglecs与神经节苷脂相互作用或不相互作用的能力，特别是GM1a，用老鼠研究神经退行性疾病，感染,和癌症，已经提出Siglecs和糖脂之间的相互作用来调节这些人类疾病。
