Autoregulation of tubulin synthesis in hepatocytes and fibroblasts.
Autoregulation of tubulin synthesis in hepatocytes and fibroblasts.
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DOI：
10.1083/jcb.101.5.1763
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发表时间：
1985-11
期刊：
影响因子：
--
通讯作者：
Kirschner MW
中科院分区：
文献类型：
--
作者：
Caron JM;Jones AL;Kirschner MW
小鼠3T6成纤维细胞和大鼠肝细胞原代培养物中的微管聚合物水平可以通过长期低剂量秋水仙胺处理细胞来控制。这种处理产生了一个相当均匀的细胞群，微管长度减少。使用该系统，我们证明了（a）微管蛋白合成速率对微管聚合物质量的微小变化（10%）敏感，（b）合成抑制百分比与可溶性微管蛋白的水平成正比。（B）合成抑制百分比与可溶性微管蛋白的水平成正比。用肝细胞进行的实验表明，微管蛋白的合成和稳定性也受到调节，以维持特定水平的微管蛋白。用秋水仙胺或其他微管解聚药物处理肝细胞，微管蛋白的半衰期从50小时减少到2小时，而稳定微管的紫杉醇增加了半衰期。为了评估改变微管聚合物质量的后果，我们分析了大鼠肝细胞中微管的控制解聚对内吞配体加工的影响，发现它对微管聚合物水平的微小变化敏感。
Microtubule polymer levels in mouse 3T6 fibroblasts and primary cultures of rat hepatocytes can be manipulated by treatment of cells with long term, low doses of colcemid. Such treatment produces a rather uniform population of cells with microtubules of reduced lengths. Using this system, we demonstrate (a) that the rate of tubulin synthesis is sensitive to small changes (10%) in microtubule polymer mass and (b) that the percent of inhibition of synthesis is proportional to the level of soluble tubulin. Experiments with hepatocytes indicate that not only synthesis but the stability of tubulin protein was also regulated to maintain a specific level of tubulin. Treatment of hepatocytes with colcemid or other microtubule-depolymerizing drugs reduced the half-life of tubulin from 50 to 2 h, whereas taxol, which stabilizes microtubules, increased the half-life. To assess the consequences of altering microtubule polymer mass, we have analyzed the effect of controlled depolymerization of microtubules in rat hepatocytes on the processing of endocytosed ligands and found it sensitive to small changes in microtubule polymer levels.