Department of Pharmacology and Molecular Sciences, Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD, 21205, USA.
Glycoconj J. 2023 Apr;40(2):159-167. doi: 10.1007/s10719-023-10101-2. Epub 2023 Jan 26.
The structure of a sialoglycan can be translated into to a biological response when it binds to a specific endogenous lectin. Among endogenous sialic acid-binding lectins in humans are those comprising the 15-member Siglec family, most of which are expressed on overlapping sets of immune cells. Endogenous Siglec ligands are sialoglycolipids (gangliosides) and/or sialoglycoproteins, on cell surfaces or in the extracellular milieu, that bind to and initiate signaling by cell surface Siglecs. In the nervous system, where gangliosides are the predominant sialoglycans, Siglec-4 (myelin-associated glycoprotein) on myelinating cells binds to gangliosides GD1a and GT1b on nerve cell axons to ensure stable and productive axon-myelin interactions. In the immune system, Siglec-7 on natural killer cells binds to gangliosides GD3 and GD2 to inhibit immune signaling. Expression of GD3 and GD2 on cancer cells can lead to tumor immune evasion. Siglec-1 (sialoadhesin, CD169) on macrophages binds to gangliosides on tumors and enveloped viruses. This may enhance antigen presentation in some cases, or increase viral distribution in others. Several other Siglecs bind to gangliosides in vitro, the biological significance of which has yet to be fully established. Gangliosides, which are found on all human cells and tissues in cell-specific distributions, are functional Siglec ligands with varied roles driving Siglec-mediated signaling.
唾液酸聚糖的结构在与特定内源性凝集素结合时可以转化为生物学反应。在人类中，内源性唾液酸结合凝集素包括由 15 个成员组成的 Siglec 家族，其中大多数在重叠的免疫细胞上表达。内源性 Siglec 配体是细胞表面或细胞外环境中的唾液酸糖脂（神经节苷脂）和/或唾液酸糖蛋白，与细胞表面 Siglecs 结合并启动信号转导。在神经系统中，神经节苷脂是主要的唾液酸聚糖，髓鞘细胞上的 Siglec-4（髓鞘相关糖蛋白）与神经细胞轴突上的神经节苷脂 GD1a 和 GT1b 结合，以确保稳定和有效的轴突-髓鞘相互作用。在免疫系统中，自然杀伤细胞上的 Siglec-7 与神经节苷脂 GD3 和 GD2 结合以抑制免疫信号。癌细胞上 GD3 和 GD2 的表达可导致肿瘤免疫逃逸。巨噬细胞上的 Siglec-1（唾液酸结合蛋白，CD169）与肿瘤和包膜病毒上的神经节苷脂结合。这在某些情况下可能增强抗原呈递，而在其他情况下则增加病毒分布。其他几种 Siglecs 在体外与神经节苷脂结合，其生物学意义尚未完全确定。神经节苷脂存在于所有人类细胞和组织中，具有特定的细胞分布，是具有不同功能的 Siglec 配体，可驱动 Siglec 介导的信号转导。
