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The Role of Calcium in Lipoprotein Release by the Low-Density Lipoprotein Receptor

机译:钙在低密度脂蛋白受体释放脂蛋白中的作用

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摘要

The LDL receptor (LDLR) mediates efficient endocytosis of VLDL, VLDL remnants, and LDL.nAs part of the uptake process, the LDLR releases lipoproteins in endosomes. Released lipoproteins arensubsequently trafficked to lysosomes for degradation, while the LDLR recycles back to the cell surface fornfurther rounds of uptake. Endosomes have at least two features that can promote lipoprotein release: an acidicnpH and low concentrations of free calcium. The relative contributions of acidic pH and low free calcium tonlipoprotein release are not known. Here, we generated fibroblasts that express either normal LDLR or annLDLR variant that is unable to employ the acid-dependent release mechanism to determine the relativencontributions of acidic pH and low free calcium on lipoprotein release. We show that endosomalnconcentrations of free calcium can drive lipoprotein release at rates that are similar to those of acid-ndependent release and that the calcium-dependent and acid-dependent mechanisms can cooperate duringnlipoprotein release.Assessment of lipoprotein uptake by these two cell lines showed that LDL uptake requiresnthe acid-dependent mechanism, while uptake of the VLDL remnant, β-VLDL, does not. We propose thatnendosomes use both the acid-dependent and calcium-dependent release mechanisms to drive lipoproteinnrelease and that the acid-dependent process is only required for LDL release.
机译:LDL受体(LDLR)介导VLDL,VLDL残留物和LDL的有效内吞作用。n作为摄取过程的一部分,LDLR在内体中释放脂蛋白。随后,释放的脂蛋白被运输到溶酶体进行降解,而LDLR循环回到细胞表面以进行进一步的摄取。内体具有至少两个可促进脂蛋白释放的功能:酸性pH和低浓度的游离钙。酸性pH和低游离钙质降钙蛋白释放的相对作用尚不清楚。在这里,我们生成了表达正常LDLR或annLDLR变体的成纤维细胞,这些变体无法采用酸依赖性释放机制来确定酸性pH和低游离钙对脂蛋白释放的相对贡献。我们表明,内皮细胞内游离钙的浓度可以以与酸依赖性释放相似的速率驱动脂蛋白释放,并且钙依赖性和酸依赖性机制可以在脂蛋白释放期间协同作用。这两个细胞系对脂蛋白摄取的评估表明: LDL的吸收需要依赖于酸的机制,而VLDL残基β-VLDL的吸收则不需要。我们建议nendosomes使用酸依赖性和钙依赖性释放机制来驱动脂蛋白的释放,并且酸依赖性过程仅对于LDL释放是必需的。

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  • 来源
    《Biochemistry》 |2009年第30期|p.7313-7324|共12页
  • 作者单位

    Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039;

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  • 正文语种 eng
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