Alexopoulou Annika N, Multhaupt Hinke A B, Couchman John R
Division of Biomedical Sciences, Imperial College London, Sir Alexander Fleming Building, Exhibition Road, London SW7 2AZ, UK.
Int J Biochem Cell Biol. 2007;39(3):505-28. doi: 10.1016/j.biocel.2006.10.014. Epub 2006 Oct 28.
Syndecans are heparan sulphate proteoglycans consisting of a type I transmembrane core protein modified by heparan sulphate and sometimes chondroitin sulphate chains. They are major proteoglycans of many organs including the vasculature, along with glypicans and matrix proteoglycans. Heparan sulphate chains have potential to interact with a wide array of ligands, including many growth factors, cytokines, chemokines and extracellular matrix molecules relevant to growth regulation in vascular repair, hypoxia, angiogenesis and immune cell function. This is consistent with the phenotypes of syndecan knock-out mice, which while viable and fertile, show deficits in tissue repair. Furthermore, there are potentially important changes in syndecan distribution and function described in a variety of human vascular diseases. The purpose of this review is to describe syndecan structure and function, consider the role of syndecan core proteins in transmembrane signalling and also their roles as co-receptors with other major classes of cell surface molecules. Current debates include potential redundancy between syndecan family members, the significance of multiple heparan sulphate interactions, regulation of the cytoskeleton and cell behaviour and the switch between promoter and inhibitor of important cell functions, resulting from protease-mediated shedding of syndecan ectodomains.
Syndecans是硫酸乙酰肝素蛋白聚糖，由一种I型跨膜核心蛋白组成，该核心蛋白被硫酸乙酰肝素修饰，有时还被硫酸软骨素链修饰。它们是包括脉管系统在内的许多器官的主要蛋白聚糖，与磷脂酰肌醇蛋白聚糖和基质蛋白聚糖一起。硫酸乙酰肝素链有可能与多种配体相互作用，包括许多与血管修复、缺氧、血管生成和免疫细胞功能中的生长调节相关的生长因子、细胞因子、趋化因子和细胞外基质分子。这与syndecan基因敲除小鼠的表型一致，这些小鼠虽然能够存活并繁殖，但在组织修复方面存在缺陷。此外，在多种人类血管疾病中描述了syndecan分布和功能的潜在重要变化。本综述的目的是描述syndecan的结构和功能，考虑syndecan核心蛋白在跨膜信号传导中的作用，以及它们作为与其他主要类型细胞表面分子的共受体的作用。当前的争论包括syndecan家族成员之间的潜在冗余、多种硫酸乙酰肝素相互作用的意义、细胞骨架和细胞行为的调节，以及由蛋白酶介导的syndecan胞外域脱落导致的重要细胞功能的启动子和抑制剂之间的转换。
