Tie Hieng Chiong, Chen Bing, Sun Xiuping, Cheng Li, Lu Lei
School of Biological Sciences, Nanyang Technological University.
Bioinformatics Institute; School of Computing, National University of Singapore.
J Vis Exp. 2017 Aug 10(126):55996. doi: 10.3791/55996.
The Golgi complex consists of serially stacked membrane cisternae which can be further categorized into sub-Golgi regions, including the cis-Golgi, medial-Golgi, trans-Golgi and trans-Golgi network. Cellular functions of the Golgi are determined by the characteristic distribution of its resident proteins. The spatial resolution of conventional light microscopy is too low to resolve sub-Golgi structure or cisternae. Thus, the immuno-gold electron microscopy is a method of choice to localize a protein at the sub-Golgi level. However, the technique and instrument are beyond the capability of most cell biology labs. We describe here our recently developed super-resolution method called Golgi protein localization by imaging centers of mass (GLIM) to systematically and quantitatively localize a Golgi protein. GLIM is based on standard fluorescence labeling protocols and conventional wide-field or confocal microscopes. It involves the calibration of chromatic-shift aberration of the microscopic system, the image acquisition and the post-acquisition analysis. The sub-Golgi localization of a test protein is quantitatively expressed as the localization quotient. There are four main advantages of GLIM; it is rapid, based on conventional methods and tools, the localization result is quantitative, and it affords ~ 30 nm practical resolution along the Golgi axis. Here we describe the detailed protocol of GLIM to localize a test Golgi protein.
高尔基体复合体由一系列堆叠的膜囊组成,这些膜囊可进一步分为高尔基体亚区,包括顺面高尔基体、中间高尔基体、反面高尔基体和反面高尔基体网络。高尔基体的细胞功能由其驻留蛋白的特征分布决定。传统光学显微镜的空间分辨率太低,无法分辨高尔基体亚结构或膜囊。因此,免疫金电子显微镜是在高尔基体亚水平定位蛋白质的一种首选方法。然而,该技术和仪器超出了大多数细胞生物学实验室的能力范围。我们在此描述我们最近开发的一种超分辨率方法,称为通过质量中心成像进行高尔基体蛋白定位(GLIM),用于系统地和定量地定位高尔基体蛋白。GLIM基于标准荧光标记方案和传统的宽场或共聚焦显微镜。它涉及显微镜系统色差像差的校准、图像采集和采集后分析。测试蛋白的高尔基体亚定位以定位商的形式定量表达。GLIM有四个主要优点:它速度快,基于传统方法和工具,定位结果是定量的,并且沿高尔基体轴提供约30nm的实际分辨率。在此我们描述GLIM定位测试高尔基体蛋白的详细方案。