The low density lipoprotein receptor-related protein functions as an Endocytic receptor for decorin
The low density lipoprotein receptor-related protein functions as an Endocytic receptor for decorin
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DOI：
10.1074/jbc.m602919200
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发表时间：
2006-10-20
影响因子：
4.8
通讯作者：
Marzolo, Maria-Paz
中科院分区：
文献类型：
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作者：
Brandan, Enrique;Retamal, Claudio;Marzolo, Maria-Paz
核心蛋白聚糖是一种富含亮氨酸的小蛋白多糖，可调节β型转化生长因子和其他生长因子的活性，从而影响多种生理和病理反应中的增殖和分化过程。因此，了解核心蛋白聚糖活性的调节机制具有广泛的意义。在这里，我们报道核心蛋白聚糖的细胞外水平由受体介导的分解代谢控制，涉及低密度脂蛋白受体家族成员，低密度脂蛋白受体相关蛋白（LRP）。我们发现核心蛋白聚糖被 C2C12 成肌细胞内吞和降解，并且通过使用短干扰 RNA 抑制 LRP 表达来阻断这两个过程。 CHO 细胞也会发生同样的情况，但 LRP 基因缺陷的 CHO 细胞则不然。最后，我们表明，转染表达含有第二或第四LRP配体结合结构域的微型LRP多肽的LRP无效CHO细胞进行核心蛋白聚糖内吞作用和溶酶体降解。这些发现表明 LRP 介导的分解代谢是核心蛋白聚糖生物活性的新控制途径，特别是其影响细胞外基质信号传导的能力。
Decorin is a small leucine-rich proteoglycan that modulates the activity of transforming growth factor type beta and other growth factors and thereby influences the processes of proliferation and differentiation in a wide array of physiological and pathological reactions. Hence, understanding the regulatory mechanisms of decorin activity has broad implications. Here we report that the extracellular levels of decorin are controlled by receptor-mediated catabolism, involving the low density lipoprotein receptor family member, low density lipoprotein receptor-related protein (LRP). We show that decorin is endocytosed and degraded by C2C12 myoblast cells and that both processes are blocked by suppressing LRP expression using short interfering RNA. The same occurs with CHO cells, but not with CHO cells genetically deficient in LRP. Finally, we show that LRP-null CHO cells, transfected to express mini-LRP polypeptides containing either the second or fourth LRP ligand-binding domains, carry out decorin endocytosis and lysosomal degradation. These findings point to LRP-mediated catabolism as a new control pathway for the biological activities of decorin, specifically for its ability to influence extracellular matrix signaling.