Schnekenburger Jürgen, Weber Ina-Alexandra, Hahn Daniela, Buchwalow Igor, Krüger Burkhard, Albrecht Elke, Domschke Wolfram, Lerch Markus M
Department of Medicine B, Westfälische Wilhelms-University, Domagkstr. 3A, 48149 Münster, Germany.
Cell Mol Life Sci. 2009 Aug;66(15):2525-37. doi: 10.1007/s00018-009-0052-0. Epub 2009 Jun 2.
The regulated secretion of pancreatic zymogens depends on a functional cytoskeleton and intracellular vesicle transport. To study the dynamics of tubulin and its motor proteins dynein and kinesin during secretion in pancreatic acinar cells, we infused rats with 0.1 mug/kg/h caerulein. Electron and fluorescence microscopy detected neither dynein nor kinesin at the apical secretory pole, nor on the surface of mature zymogen granules. After 30 min of secretagogue stimulation, kinesin and the Golgi marker protein 58 K were reallocated towards the apical plasma membrane and association of kinesin with tubulin was enhanced. Disruption of acinar cell microtubules had no effect on initial caerulein-induced amylase release but completely blocked secretion during a second stimulus. Our results suggest that mature zymogen granule exocytosis is independent of intact microtubules, kinesin and dynein. However, microtubule-dependent mechanisms seem to be important for the replenishment of secretory vesicles by redistribution of Golgi elements towards the apical cell pole.
胰腺酶原的调节性分泌依赖于功能性细胞骨架和细胞内囊泡运输。为了研究胰腺腺泡细胞分泌过程中微管蛋白及其驱动蛋白动力蛋白和驱动蛋白的动力学,我们以0.1微克/千克/小时的剂量给大鼠输注蛙皮素。电子显微镜和荧光显微镜在顶端分泌极以及成熟酶原颗粒表面均未检测到动力蛋白和驱动蛋白。促分泌剂刺激30分钟后,驱动蛋白和高尔基体标记蛋白58K重新分布至顶端质膜,且驱动蛋白与微管蛋白的结合增强。腺泡细胞微管的破坏对初始蛙皮素诱导的淀粉酶释放没有影响,但在第二次刺激时完全阻断了分泌。我们的结果表明,成熟酶原颗粒的胞吐作用独立于完整的微管、驱动蛋白和动力蛋白。然而,微管依赖性机制似乎对于通过高尔基体元件向顶端细胞极的重新分布来补充分泌囊泡很重要。