绘制表皮生长因子受体-1的地图,用校准的三维扩展显微镜工具包对内基因组中的分类域进行排序
Tayla Shakespeare1,2,3, Rajpinder S Seehra1, Neftali Flores Rodriguez4
1School of Biosciences, Faculty of Science, The University of Sheffield, Sheffield S10 2TN South Yorkshire, U.K.
ACS nano
|March 17, 2026
概括
研究人员开发了一种新的3D扩展显微镜 (ExM) 方法,以准确可视化纳米级内体蛋白质集群. 这种技术纠正了扭曲,使得可以精确地测量细胞内部分,如内体和表皮生长因子受体-1 (EGFR1) 分类.
科学领域:
- 细胞生物学 细胞生物学
- 显微镜的使用方法
- 纳米技术 纳米技术
背景情况:
- 内基因组对于分类和回收细胞表面受体,如EGFR1.1,至关重要.
- 内体内的纳米级相互作用至关重要,但很难用当前的显微镜可视化.
- 以前的方法在精确的3D可视化小细胞内隔间方面遇到了困难.
研究的目的:
- 适应和验证扩展显微镜 (ExM) 用于可视化和量化内体蛋白质纳米集群.
- 开发一种方法来纠正内分泌体的ExM图像中的膨胀扭曲.
- 为研究内体动力学中的分子级事件提供定量框架.
主要方法:
- 适应扩展显微镜 (ExM) 用于在RPE-1细胞中3D可视化内体蛋白质.
- 开发了使用光流原理进行3D扭曲分析,以纠正水凝膨胀异构.
- 引入了一种蛋白质纳米,用于校准局部纳米扩张因子.
- 应用了EGF/EGFR1的脉冲追踪标记和多重3D空气扫描显微镜.
- 利用体积追踪管道来分析蛋白质密度的变化.
主要成果:
- 鉴定了细胞质区域的不充分扩张和标准ExM中内分体大小/距离的高估.
- 使用蛋白质纳米记者成功校准了ExM图像.
- 可视化了EGF和EGFR1的内部化和排序动态.
- 在内体内部观察到EGF/EGFR1的丰富,并在内体早期成熟期间观察到Rab5a的积累.
结论:
- 开发的多重3DExM工具包使纳米级内体结构的准确可视化和测量成为可能.
- 这种定量框架克服了小型有机体的传统和超分辨率显微镜的局限性.
- 提供了对EGFR1分类和内分体成熟的分子机制的新见解.
相关概念视频
Receptor Downregulation in MVBs
2.9K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.9K
The Early Endosome: Endocytosis of Transferrin
5.1K
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
5.1K


