MONENSIN INTERRUPTS THE RECYCLING OF LOW-DENSITY LIPOPROTEIN RECEPTORS IN HUMAN-FIBROBLASTS
MONENSIN INTERRUPTS THE RECYCLING OF LOW-DENSITY LIPOPROTEIN RECEPTORS IN HUMAN-FIBROBLASTS
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DOI：
10.1016/0092-8674(81)90340-8
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发表时间：
1981-01-01
期刊：
影响因子：
64.5
通讯作者：
BROWN, MS
中科院分区：
文献类型：
--
作者：
BASU, SK;GOLDSTEIN, JL;BROWN, MS
在培养的人成纤维细胞中，每个LDL [低密度脂蛋白]受体介导. apprx的内化。每20小时100粒LDL。有证据表明，低密度脂蛋白受体的再利用涉及受体进出细胞的再循环，而羧基离子载体莫能菌素阻止受体返回表面。在莫能菌素和LDL的存在下，75%的受体在15分钟内从细胞表面消失，> 90%在60分钟内消失。离开表面的受体被困在细胞内的核周空泡内，通过使用LDL受体的抗体的间接免疫荧光可视化。在不存在LDL的情况下，莫能菌素引起. apprx. 50%的受体被困胞内15分钟内。莫能菌素处理后，表面上仍然存在的受体可以被困在细胞内，如果LDL随后加入在持续存在的莫能菌素。莫能菌素没有降低内化缺陷型家族性高胆固醇血症患者成纤维细胞表面LDL受体。在这些突变细胞中，LDL受体不定位于被膜小凹。目前的数据被解释为表明：在正常成纤维细胞中。在没有LDL的情况下，50%的表面LDL受体不断循环进出细胞;剩余的50%的表面受体可以通过LDL的存在被诱导循环;莫能菌素通过阻止受体返回表面来中断这种循环，导致受体在细胞内积累。
In cultured human fibroblasts, each LDL [low density lipoprotein] receptor mediates the internalization of .apprx. 100 particles of LDL every 20 h. Evidence is provided that the reutilization of LDL receptors involves the recycling of receptors into and out of the cell, and the carboxylic ionophore monensin blocks the return of the receptors to the surface. In the presence of monensin and LDL, 75% of the receptors disappeared from the cell surface within 15 min and > 90% disappeared within 60 min. The receptors that left the surface were trapped intracellularly within perinuclear vacuoles, as visualized by indirect immunofluorescence with the use of an antibody to the LDL receptor. In the absence of LDL, monensin caused .apprx. 50% of the receptors to be trapped intracellularly within 15 min. The receptors that remained on the surface after monensin treatment could be trapped within the cell if LDL was added subsequently in the continued presence of monensin. Monensin did not decrease surface LDL receptors in fibroblasts from a patient with the internalization-defective form of familial hypercholesterolemia. In these mutant cells, LDL receptors are not localized to coated pits. The current data are interpreted to indicate that: in normal fibroblasts .apprx. 50% of surface LDL receptors recycle continuously into and out of the cell in the absence of LDL; the remaining 50% of surface receptors can be induced to recycle by the presence of LDL; monensin interrupts this recycling by preventing the receptor from returning to the surface, causing the receptors to accumulate within the cell.