Schönherr E, Zhao B, Hausser H, Müller M, Langer C, Wagner W D, Goldberg I J, Kresse H
Institutes of Physiological Chemistry and Pathobiochemistry, University of Münster, Germany.
Eur J Cell Biol. 2000 Oct;79(10):689-96. doi: 10.1078/0171-9335-00103.
According to numerous studies low-density lipoproteins (LDL) are supposed to interact with the glycosaminoglycan chain(s) of proteoglycans, e.g. with decorin and biglycan, which themselves are subject to receptor-mediated endocytosis. We tested, therefore, whether complexes of LDL and small proteoglycans can be endocytosed by either the LDL- or the small proteoglycan uptake mechanism. However, neither was the endocytosis of LDL significantly influenced by proteoglycans nor that of proteoglycans by LDL. This negative result could be explained by the observation that in vitro complex formation takes place only in buffers of low ionic strength. Under physiological conditions additional molecules may be necessary for complex stabilization. Lipoprotein lipase (LpL) which binds LDL was also able to interact with high affinity with decorin and its glycosaminoglycan-free core protein, both interactions being heparin-sensitive. Regardless of the presence or absence of LDL, LpL stimulated the endocytosis of decorin 1.5-fold, whereas LpL mediated a 4-fold stimulation of LDL uptake in the absence of decorin. No significant additional effect was seen in the presence of small concentrations of proteoglycans whereas in the presence of 1 microM decorin the endocytosis of [125I]LDL was reduced in normal as well as in LDL receptor-deficient fibroblasts. These observations could best be explained by assuming that LpL/LDL complexes are internalized upon binding to membrane-associated heparan sulphate and that small proteoglycans interfere with this process. It could not be ruled out, however, that a small proportion of the complexes is also taken up by the small proteoglycan receptor.
根据大量研究，低密度脂蛋白（LDL）被认为可与蛋白聚糖的糖胺聚糖链相互作用，例如与核心蛋白聚糖和双糖链蛋白聚糖相互作用，而它们自身也会经历受体介导的内吞作用。因此，我们测试了LDL与小蛋白聚糖的复合物是否能通过LDL或小蛋白聚糖摄取机制被内吞。然而，蛋白聚糖对LDL的内吞作用以及LDL对蛋白聚糖的内吞作用均未产生显著影响。这一负面结果可以通过以下观察结果来解释：体外复合物的形成仅发生在低离子强度的缓冲液中。在生理条件下，可能需要其他分子来稳定复合物。结合LDL的脂蛋白脂肪酶（LpL）也能够与核心蛋白聚糖及其无糖胺聚糖的核心蛋白以高亲和力相互作用，这两种相互作用均对肝素敏感。无论是否存在LDL，LpL均可使核心蛋白聚糖的内吞作用增强1.5倍，而在不存在核心蛋白聚糖的情况下，LpL介导的LDL摄取增强4倍。在存在低浓度蛋白聚糖时未观察到明显的额外效应，而在存在1 microM核心蛋白聚糖时，正常和成纤维细胞低密度脂蛋白受体缺陷的成纤维细胞中[125I]LDL的内吞作用均降低。这些观察结果最好通过假设LpL/LDL复合物在与膜相关的硫酸乙酰肝素结合后被内化，以及小蛋白聚糖会干扰这一过程来解释。然而，不能排除一小部分复合物也被小蛋白聚糖受体摄取的可能性。
