Pharmacological Sequestration of Intracellular Cholesterol in Late Endosomes Disrupts Ruffled Border Formation in Osteoclasts
Pharmacological Sequestration of Intracellular Cholesterol in Late Endosomes Disrupts Ruffled Border Formation in Osteoclasts
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DOI：
10.1359/jbmr.051204
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发表时间：
2005-12
影响因子：
6.2
通讯作者：
Haibo Zhao;H. Väänänen
中科院分区：
文献类型：
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作者：
Haibo Zhao;H. Väänänen
我们发现，皱褶边缘缺乏晚期内体脂质，LBPA，但富含胆固醇。疏水胺U18666 A导致破骨细胞中LBPA+晚期内体中胆固醇积聚。U18666 A阻断了组织蛋白酶K和液泡H+-ATP酶在皱褶边缘的特异性靶向作用。从基底外侧膜到吸收细胞器的膜运输途径也被抑制剂阻止。这些结果表明胆固醇稳态调节晚期内体/溶酶体运输和再吸收破骨细胞的极化分泌。
We showed that the ruffled border lacks a late endosomal lipid, LBPA, but is enriched in cholesterol. A hydrophobic amine, U18666A, causes cholesterol accumulation in LBPA+ late endosomes in osteoclasts. Specific targeting of cathepsin K and the vacuolar H+‐ATPase at the ruffled border is blocked by U18666A. A membrane trafficking pathway from baso‐lateral membrane toward the resorptive organelle is also arrested by the inhibitor. These results indicate cholesterol homeostasis regulates late endosomal/lysosomal trafficking and polarized secretion in resorbing osteoclasts.