Colchicine analogues that bind reversibly to tubulin define microtubular requirements for newly synthesized protein secretion in rat lacrimal gland.

Colchicine analogues that bind reversibly to tubulin define microtubular requirements for newly synthesized protein secretion in rat lacrimal gland.
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可逆地与微管蛋白结合的秋水仙碱类似物定义了大鼠泪腺中新合成蛋白质分泌的微管需求。

DOI:
10.1073/pnas.86.12.4515
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发表时间:
1989
影响因子:
11.1
通讯作者:
Rossignol,B
Rossignol,B
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Herman,G;Busson,S;Gorbunoff,MJ;Mauduit,P;Timasheff,SN;Rossignol,B

文献摘要

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相似文献

微管在大鼠泪腺3 H-标记的蛋白质分泌的作用,探讨了通过使用秋水仙碱和它的类似物,可逆地结合到微管蛋白。这些类似物是2-甲氧基-5-(2,3,4,4 '-三甲氧基苯基)-2,4,6-环庚三烯-1-酮和2,3,4,4'-四甲氧基-1,1 '-联苯,后者是为这些研究而合成的。免疫荧光显示,未经处理的外分泌腺泡细胞包含一个完整的微管网络,这是完全取消药物添加。随后的药物去除恢复了两种可逆结合药物的网络-联苯的速度更快,但秋水仙碱的情况并非如此。通过在不同阶段加入三种药物来检查蛋白质分泌过程-脉冲前孵育、脉冲、成熟、颗粒的顶端储存和胆碱能刺激下的放电。与微管网络恢复的动力学,这两个可逆结合的药物不同的比较,导致的结论是,微管系统的分泌的成熟阶段是至关重要的。
The role of microtubules in 3H-labeled protein secretion in rat lacrimal glands was probed by the use of colchicine and two of its analogues that reversibly bind to tubulin. These analogues were 2-methoxy-5-(2,3,4,4'-trimethoxyphenyl)-2,4,6-cycloheptatriene-1-o ne and 2,3,4,4'-tetramethoxy-1,1'-biphenyl, the latter having been synthesized for these studies. Immunofluorescence revealed that untreated exocrine acinar cells contained an intact microtubule network, which was totally abolished by drug addition. Subsequent drug removal restored the network for the two reversibly binding drugs--more rapidly so for the biphenyl, but this was not the case with colchicine. The protein-secretory process was examined by adding the three drugs at various stages--prepulse incubation, pulse, maturation, apical storage of granules, and discharge under cholinergic stimulation. Comparison with the kinetics of microtubular network restoration, which differed for the two reversibly binding drugs, led to the conclusion that the microtubular system is critical to the maturation phase of secretion.