Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin
Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin
复制标题
DOI：
10.1083/jcb.200511134
复制
发表时间：
2006-09-25
影响因子：
7.8
通讯作者：
Laurie, Gordon W.
中科院分区：
文献类型：
--
作者：
Ma, Peisong;Beck, Shannon L.;Laurie, Gordon W.
细胞表面硫酸乙酰肝素 (HS) 蛋白聚糖是细胞迁移、有丝分裂、分泌和炎症活性的富含碳水化合物的调节剂，可将可溶性肝素结合生长因子（例如成纤维细胞生长因子、Wnt、Hh、转化生长因子 β、双调蛋白和肝细胞生长因子）结合并呈递到各自的信号传导受体。我们证明，syndecan-1 (SDC1) 的去糖化核心蛋白（而不是 HS 链、SDC2 或 -4）似乎靶向上皮选择性原分泌促有丝分裂原乳泌素。该机制中一个重要且新颖的步骤是，结合需要先通过内源性乙酰肝素酶部分或完全去除 HS 链。这将泪泌素的活性限制在乙酰肝素酶占主导地位的部位，例如外分泌细胞迁移、分泌、更新和炎症的部位。结合由lacritin 的C 端促有丝分裂结构域和SDC1 的N 端相互指定。莫迪乙酰肝素酶。后者的阳离子将广泛表达的 HS 蛋白多糖转化为高度选择性的表面结合蛋白。这个通过 HS 蛋白聚糖的细胞外修饰实现细胞特化的新例子对发育、体内平衡和疾病具有广泛的影响。
Cell surface heparan sulfate (HS) proteoglycans are carbohydrate-rich regulators of cell migratory, mitogenic, secretory, and inflammatory activity that bind and present soluble heparin-binding growth factors (e.g., fibroblast growth factor, Wnt, Hh, transforming growth factor beta, amphiregulin, and hepatocyte growth factor) to their respective signaling receptors. We demonstrate that the deglycanated core protein of syndecan-1 (SDC1) and not HS chains nor SDC2 or -4, appears to target the epithelial selective prosecretory mitogen lacritin. An important and novel step in this mechanism is that binding necessitates prior partial or complete removal of HS chains by endogenous heparanase. This limits lacritin activity to sites where heparanase appears to predominate, such as sites of exocrine cell migration, secretion, renewal, and inflammation. Binding is mutually specified by lacritin's C-terminal mitogenic domain and SDC1's N terminus. Heparanase modi. cation of the latter transforms a widely expressed HS proteoglycan into a highly selective surface-binding protein. This novel example of cell specification through extracellular modification of an HS proteoglycan has broad implications in development, homeostasis, and disease.