The role of calcium in lipoprotein release by the low-density lipoprotein receptor.
The role of calcium in lipoprotein release by the low-density lipoprotein receptor.
复制标题
钙在低密度脂蛋白受体释放脂蛋白中的作用。
DOI：
10.1021/bi900214u
复制
发表时间：
2009
期刊：
影响因子：
2.9
通讯作者：
Michaely,Peter
中科院分区：
文献类型：
--
作者：
Zhao,Zhenze;Michaely,Peter
LDL受体（LDLR）介导VLDL、VLDL残余物和LDL的有效内吞作用。作为摄取过程的一部分，LDLR在内体中释放脂蛋白。释放的脂蛋白随后被运输到溶酶体进行降解，而LDLR则返回细胞表面进行进一步的摄取。内体具有至少两个可以促进脂蛋白释放的特征：酸性pH和低浓度的游离钙。酸性pH和低游离钙对脂蛋白释放的相对贡献尚不清楚。在这里，我们产生的成纤维细胞表达正常的LDLR或LDLR的变体，是无法采用酸依赖性释放机制，以确定相对贡献的酸性pH值和低游离钙脂蛋白释放。我们发现，内体浓度的游离钙可以驱动脂蛋白释放的速率是类似的酸依赖性释放和钙依赖性和酸依赖性机制可以合作，在脂蛋白释放。对这两种细胞系的脂蛋白摄取的评估表明，LDL摄取需要酸依赖性机制，而VLDL残余物β-VLDL的摄取则不需要。我们认为，内体使用酸依赖性和钙依赖性释放机制来驱动脂蛋白释放，并且酸依赖性过程仅用于LDL释放。
The LDL receptor (LDLR) mediates efficient endocytosis of VLDL, VLDL remnants, and LDL. As part of the uptake process, the LDLR releases lipoproteins in endosomes. Released lipoproteins are subsequently trafficked to lysosomes for degradation, while the LDLR recycles back to the cell surface for further rounds of uptake. Endosomes have at least two features that can promote lipoprotein release: an acidic pH and low concentrations of free calcium. The relative contributions of acidic pH and low free calcium to lipoprotein release are not known. Here, we generated fibroblasts that express either normal LDLR or an LDLR variant that is unable to employ the acid-dependent release mechanism to determine the relative contributions of acidic pH and low free calcium on lipoprotein release. We show that endosomal concentrations of free calcium can drive lipoprotein release at rates that are similar to those of acid-dependent release and that the calcium-dependent and acid-dependent mechanisms can cooperate during lipoprotein release. Assessment of lipoprotein uptake by these two cell lines showed that LDL uptake requires the acid-dependent mechanism, while uptake of the VLDL remnant, β-VLDL, does not. We propose that endosomes use both the acid-dependent and calcium-dependent release mechanisms to drive lipoprotein release and that the acid-dependent process is only required for LDL release.