Intracellular Membrane Trafficking Unit and Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4340, USA.
Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13552-7. doi: 10.1073/pnas.1016778108. Epub 2011 Aug 1.
The regulation and the dynamics of membrane trafficking events have been studied primarily in in vitro models that often do not fully reflect the functional complexity found in a living multicellular organism. Here we used intravital microscopy in the salivary glands of live rodents to investigate regulated exocytosis, a fundamental process in all of the secretory organs. We found that β-adrenergic stimulation elicits exocytosis of large secretory granules, which gradually collapse with the apical plasma membrane without any evidence of compound exocytosis, as was previously described. Furthermore, we show that the driving force required to complete the collapse of the granules is provided by the recruitment of F-actin and nonmuscle myosin II on the granule membranes that is triggered upon fusion with the plasma membrane. Our results provide information on the machinery controlling regulated secretion and show that intravital microscopy provides unique opportunities to address fundamental questions in cell biology under physiological conditions.
膜运输事件的调节和动力学主要在体外模型中进行研究，这些模型通常不能完全反映在活多细胞生物体中发现的功能复杂性。在这里，我们使用活体啮齿动物唾液腺中的活体显微镜检查来研究受调节的胞吐作用，这是所有分泌器官的基本过程。我们发现，β-肾上腺素能刺激引发大分泌颗粒的胞吐作用，这些颗粒逐渐与顶端质膜塌陷，没有任何先前描述的复合胞吐作用的证据。此外，我们表明，完成颗粒塌陷所需的驱动力是由颗粒膜上的 F-肌动蛋白和非肌肉肌球蛋白 II 的募集提供的，这种募集是在与质膜融合时触发的。我们的结果提供了关于控制受调节分泌的机制的信息，并表明活体显微镜检查为在生理条件下解决细胞生物学中的基本问题提供了独特的机会。
