Dynamin is functionally coupled to insulin granule exocytosis
Dynamin is functionally coupled to insulin granule exocytosis
复制标题
DOI：
10.1074/jbc.m703402200
复制
发表时间：
2007-11-16
影响因子：
4.8
通讯作者：
Hou, June Chunqiu
中科院分区：
文献类型：
--
作者：
Min, Le;Leung, Yuk M.;Hou, June Chunqiu
胰岛素颗粒整合膜蛋白标记物噬菌蛋白绿色荧光蛋白与 Min6B1 β 细胞分泌颗粒中的胰岛素共定位，但在葡萄糖刺激后不发生质膜易位。令人惊讶的是，尽管显性干扰动力突变体（Dyn/K44A）的表达抑制转铁蛋白受体内吞作用，但它对基础或促分泌素刺激状态下的噬菌蛋白绿色荧光蛋白定位没有影响。相比之下，Dyn/K44A 与人生长激素作为胰岛素分泌标记物的共表达导致葡萄糖、KCl 和多种促分泌剂的组合对人生长激素释放的显着抑制。此外，连续脉冲去极化刺激细胞表面电容的增加，这种增加在表达 Dyn/K44A 的细胞中也被阻断。类似地，小干扰RNA介导的动力敲低导致葡萄糖刺激的胰岛素分泌的显着抑制。总之，这些数据表明存在选择性的胰岛素释放机制。此外，这些数据表明胞吞作用和胞吐作用在β细胞胰岛素分泌调节中的耦合。
The insulin granule integral membrane protein marker phogrin-green fluorescent protein was co-localized with insulin in Min6B1 beta-cell secretory granules but did not undergo plasma membrane translocation following glucose stimulation. Surprisingly, although expression of a dominant-interfering dynamin mutant (Dyn/K44A) inhibited transferrin receptor endocytosis, it had no effect on phogrin-green fluorescent protein localization in the basal or secretagogue-stimulated state. By contrast, co-expression of Dyn/ K44A with human growth hormone as an insulin secretory marker resulted in a marked inhibition of human growth hormone release by glucose, KCl, and a combination of multiple secretagogues. Moreover, serial pulse depolarization stimulated an increase in cell surface capacitance that was also blocked in cells expressing Dyn/ K44A. Similarly, small interference RNA-mediated knockdown of dynamin resulted in marked inhibition of glucose-stimulated insulin secretion. Together, these data suggest the presence of a selective kiss and run mechanism of insulin release. Moreover, these data indicate a coupling between endocytosis and exocytosis in the regulation of beta-cell insulin secretion.