一种家族性高胆固醇血症的新型细胞表型,原因是LDL受体偏振向的缺陷
U M Koivisto1, A L Hubbard, I Mellman
1Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar Street, PO Box 208002, New Haven, CT 06520, USA.
Cell
|June 8, 2001
概括
在LDL受体的突变导致家族高胆固醇血症通过误导受体到细胞表面,损害胆固醇清除. 这凸显了蛋白质向信号在人类疾病中的关键作用.
科学领域:
- 细胞生物学 细胞生物学
- 分子遗传学 分子遗传学
- 皮质细胞的极性
背景情况:
- 在极化表皮细胞中,基底侧向膜蛋白依赖于细胞质域分类信号.
- 家庭性高胆固醇血 (FH) - - 图尔库的LDL受体等位基因涉及影响基侧向的突变.
研究的目的:
- 研究特定的LDL受体突变对蛋白质向的影响及其与家族性高胆固醇血症的联系.
- 确认基底侧向信号在维持上皮细胞极性和疾病发病过程中的作用.
主要方法:
- 利用马丁-达比犬 (MDCK) 和肝上皮细胞来研究受体局部化.
- 在LDL受体缺乏的小鼠中使用病毒编码的突变受体来评估胆固醇清除.
主要成果:
- 在这两种细胞类型中,突变的LDL受体被错误地定位到顶端表面.
- 观察到从底侧/侧侧侧面的LDL细胞内细胞减少.
- 突变受体未能在体内调解胆固醇清除,这表明偏振表达有缺陷.
结论:
- 在LDL受体的基底侧向信号的缺陷可以导致家族性高胆固醇血症.
- 这项研究为这些信号在上皮细胞极性和疾病中的重要性提供了遗传确认.
- 在肝细胞中改变的LDL受体局部化有助于高胆固醇血症的发病.
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