Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as a receptor for interstitial matrix.
Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as a receptor for interstitial matrix.
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DOI：
10.1083/jcb.106.2.423
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发表时间：
1988-02
期刊：
影响因子：
--
通讯作者：
Bernfield M
中科院分区：
文献类型：
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作者：
Saunders S;Bernfield M
NMuMG小鼠乳腺上皮细胞表面的蛋白多糖（PG）由至少两个功能结构域组成，一个是将PG锚定在质膜上的膜插入结构域，另一个是胰蛋白酶释放的外结构域，包含肝素和硫酸软骨素链。外结构域将细胞与I、III和V型胶原结合，但不与IV型胶原结合，并被认为是一种基质受体。由于肝素与黏附糖蛋白纤维连接蛋白（一种间质基质成分）和层粘连蛋白（一种基层成分）结合，我们想知道细胞表面的PG是否也与这些分子结合。与纤维连接蛋白结合的胰蛋白酶或EDTA收获的细胞；GRGDS肽抑制胰蛋白酶释放细胞的结合，而肝素不抑制胰蛋白酶释放细胞的结合，而edta释放细胞的结合仅被GRDS和肝素联合抑制，提示两种不同的细胞结合机制。在GRGDS存在的情况下，edta释放的细胞通过细胞表面PG与纤维连接蛋白结合，通过细胞表面PG与纤维连接蛋白的cooh末端肝素结合域结合。与纤维连接蛋白的结合相反，edta释放的细胞在相同的实验条件下不与层粘连蛋白结合。脂质体含有分离的完整细胞表面PG模拟整个细胞的结合。这些结果表明，乳腺上皮细胞至少有两种不同的纤维连接蛋白细胞表面受体：一种是胰蛋白酶抗性分子，它将细胞与RGD序列结合；另一种是胰蛋白酶不稳定的富含硫酸肝素的PG，它将细胞与cooh末端肝素结合域结合。由于细胞表面PG将细胞与间质胶原（I型、III型和V型）和纤维连接蛋白结合，但不与基底层胶原（IV型）或层粘连蛋白结合，因此我们得出结论，细胞表面PG是上皮细胞上特异性的间质基质成分受体。
The proteoglycan (PG) on the surface of NMuMG mouse mammary epithelial cells consists of at least two functional domains, a membrane- intercalated domain which anchors the PG to the plasma membrane, and a trypsin-releasable ectodomain which bears both heparan and chondroitin sulfate chains. The ectodomain binds cells to collagen types I, III, and V, but not IV, and has been proposed to be a matrix receptor. Because heparin binds to the adhesive glycoproteins fibronectin, an interstitial matrix component, and laminin, a basal lamina component, we asked whether the cell surface PG also binds these molecules. Cells harvested with either trypsin or EDTA bound to fibronectin; binding of trypsin-released cells was inhibited by the peptide GRGDS but not by heparin, whereas binding of EDTA-released cells was inhibited only by a combination of GRDS and heparin, suggesting two distinct cell binding mechanisms. In the presence of GRGDS, the EDTA-released cells bound to fibronectin via the cell surface PG. Binding via the cell surface PG was to the COOH-terminal heparin binding domain of fibronectin. In contrast with the binding to fibronectin, EDTA-released cells did not bind to laminin under identical assay conditions. Liposomes containing the isolated intact cell surface PG mimic the binding of whole cells. These results indicate that the mammary epithelial cells have at least two distinct cell surface receptors for fibronectin: a trypsin- resistant molecule that binds cells to the sequence RGD and a trypsin- labile, heparan sulfate-rich PG that binds cells to the COOH-terminal heparin binding domain. Because the cell surface PG binds cells to the interstitial collagens (types I, III, and V) and to fibronectin, but not to basal lamina collagen (type IV) or laminin, we conclude that the cell surface PG is a receptor on epithelial cells specific for interstitial matrix components.