The syndecan family of proteoglycans - Novel receptors mediating internalization of atherogenic lipoproteins in vitro
The syndecan family of proteoglycans - Novel receptors mediating internalization of atherogenic lipoproteins in vitro
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DOI：
10.1172/jci119685
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发表时间：
1997-09-15
影响因子：
15.9
通讯作者：
Williams, KJ
中科院分区：
文献类型：
--
作者：
Fuki, IV;Kuhn, KM;Williams, KJ
细胞表面硫酸乙酰肝素蛋白多糖已被证明参与脂蛋白分解代谢，但以前还没有研究过特定蛋白多糖类别的作用。在这里，我们研究了Syndecan蛋白多糖家族的参与。首先，将几种Syndecan核心蛋白的表达载体导入CHO细胞后，细胞结合能力和富含脂蛋白脂酶(一种肝素结合蛋白)的脂蛋白的降解都得到了平行的增加。第二，嵌合结构FCR-Synd1，它由Ig G Fc受体Ia的胞外区与Syndecan-1的高度保守的跨膜区和细胞质区相连，在配体聚集触发的过程中直接介导有效的内化。第三，通过Syndecan-1内化富含脂肪酶的脂蛋白和通过嵌合体内化聚集的IgG表现出相同的动力学(t(1/2)=1h)和对破坏微丝的细胞松弛素B和抑制酪氨酸激酶的染料木素具有相同的剂量-反应敏感性。相反，受体相关蛋白的内化通过包被的凹坑进行，表现出t(1/2)和15分钟，对细胞松弛素B有限敏感，对金雀异黄素完全不敏感。因此，Syndecan蛋白多糖可以通过一种不同于包被小窝的途径直接介导配体的分解代谢，并可能在体内作为致动脉粥样硬化脂蛋白和其他配体的受体。
Cell-surface heparan sulfate proteoglycans have been shown to participate in lipoprotein catabolism, but the roles of specific proteoglycan classes have not been examined previously. Here, we studied the involvement of the syndecan proteoglycan family. First, transfection of CHO cells with expression vectors for several syndecan core proteins produced parallel increases in the cell association and degradation of lipoproteins enriched in lipoprotein lipase, a heparan-binding protein. Second, a chimeric construct, FcR-Synd1, that consists of the ectodomain of the IgG Fc receptor Ia linked to the highly conserved transmembrane and cytoplasmic domains of syndecan-1 directly mediated efficient internalization, in a process triggered by ligand clustering. Third, internalization of lipase-enriched lipoproteins via syndecan-1 and of clustered IgGs via the chimera showed identical kinetics (t(1/2) = 1 h) and identical dose-response sensitivities to cytochalasin B, which disrupts microfilaments, and to genistein, which inhibits tyrosine kinases. In contrast, internalization of the receptor-associated protein, which proceeds via coated pits, showed a t(1/2) < 15 min, Limited sensitivity to cytochalasin B, and complete insensitivity to genistein. Thus, syndecan proteoglycans can directly mediate ligand catabolism through a pathway with characteristics distinct from coated pits, and might act as receptors for atherogenic lipoproteins and other ligands in vivo.