University of North Carolina at Chapel Hill, Department of Cell Biology and Physiology, Chapel Hill, NC 27599, USA.
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
J Cell Sci. 2024 Oct 15;137(20). doi: 10.1242/jcs.261828. Epub 2024 Jun 7.
Exocytosis is a fundamental process used by eukaryotes to regulate the composition of the plasma membrane and facilitate cell-cell communication. To investigate exocytosis in neuronal morphogenesis, previously we developed computational tools with a graphical user interface to enable the automatic detection and analysis of exocytic events from fluorescence timelapse images. Although these tools were useful, we found the code was brittle and not easily adapted to different experimental conditions. Here, we developed and validated a robust and versatile toolkit, named pHusion, for the analysis of exocytosis, written in ImageTank, a graphical programming language that combines image visualization and numerical methods. We tested pHusion using a variety of imaging modalities and pH-sensitive fluorophores, diverse cell types and various exocytic markers, to generate a flexible and intuitive package. Using this system, we show that VAMP3-mediated exocytosis occurs 30-times more frequently in melanoma cells compared with primary oligodendrocytes, that VAMP2-mediated fusion events in mature rat hippocampal neurons are longer lasting than those in immature murine cortical neurons, and that exocytic events are clustered in space yet random in time in developing cortical neurons.
胞吐作用是真核生物用来调节质膜组成并促进细胞间通讯的基本过程。为了研究神经元形态发生中的胞吐作用,我们之前开发了具有图形用户界面的计算工具,以实现从荧光时程图像中自动检测和分析胞吐事件。虽然这些工具很有用,但我们发现代码易碎,不易适应不同的实验条件。在这里,我们开发并验证了一个名为 pHusion 的强大而通用的工具包,用于分析胞吐作用,该工具包使用 ImageTank 编写,这是一种图形编程语言,它将图像可视化和数值方法结合在一起。我们使用各种成像模式和 pH 敏感荧光染料、不同的细胞类型和各种胞吐标记物来测试 pHusion,以生成灵活直观的软件包。使用该系统,我们发现与原代少突胶质细胞相比,黑色素瘤细胞中 VAMP3 介导的胞吐作用发生的频率高 30 倍,成熟大鼠海马神经元中 VAMP2 介导的融合事件持续时间比不成熟的鼠皮质神经元长,并且胞吐事件在发育中的皮质神经元中空间上聚类但时间上随机。