Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
J Biol Chem. 2024 Jul;300(7):107482. doi: 10.1016/j.jbc.2024.107482. Epub 2024 Jun 17.
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.
唾液酸结合免疫球蛋白样凝集素（Siglecs）是一类细胞表面受体，其功能与它们的唾液酸糖缀合物配体的结合有关。最近，我们开发了一种优化的脂质体配方，并使用它来研究人类 Siglecs（hSiglec）与一系列神经节苷脂的结合。动物模型，特别是鼠模型，被用于了解人类生物学；然而，种属特异性差异可能会使结果的解释变得复杂。在这里，我们使用我们优化的脂质体配方来剖析鼠 Siglecs（mSiglecs）与神经节苷脂之间的相互作用，以评估 mSiglecs 作为更好地理解 hSiglec-神经节苷脂相互作用的生物学作用的替代物的适宜性。使用我们优化的脂质体配方，我们发现，尽管 mSiglec-1、-E、-F 和 -15 与它们的人类对应物一样，结合多种神经节苷脂，但神经节苷脂结合在小鼠和人类之间通常是保守的。然而，与 hSiglecs 不同的是，我们观察到 mSiglecs 与神经节苷脂 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，特别是 GM1a，相互作用或不相互作用的能力，对使用小鼠来研究神经退行性疾病、感染和癌症具有影响，因为已经提出 Siglecs 和糖脂之间的相互作用可以调节这些人类疾病。
