Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands.
ACS Chem Biol. 2012 Jan 20;7(1):139-49. doi: 10.1021/cb200326g. Epub 2011 Nov 14.
Understanding the molecular mechanisms that shape an effective cellular response is a fundamental question in biology. Biochemical measurements have revealed critical information about the order of protein-protein interactions along signaling cascades but lack the resolution to determine kinetics and localization of interactions on the plasma membrane. Furthermore, the local membrane environment influences membrane receptor distributions and dynamics, which in turn influences signal transduction. To measure dynamic protein interactions and elucidate the consequences of membrane architecture interplay, direct measurements at high spatiotemporal resolution are needed. In this review, we discuss the biochemical principles regulating membrane nanodomain formation and protein function, ranging from the lipid nanoenvironment to the cortical cytoskeleton. We also discuss recent advances in fluorescence microscopy that are making it possible to quantify protein organization and biochemical events at the nanoscale in the living cell membrane.
了解塑造有效细胞反应的分子机制是生物学中的一个基本问题。生化测量已经揭示了沿信号级联的蛋白质-蛋白质相互作用的顺序的关键信息，但缺乏确定质膜上相互作用的动力学和定位的分辨率。此外，局部膜环境会影响膜受体的分布和动态，从而影响信号转导。为了测量动态蛋白质相互作用并阐明膜结构相互作用的后果，需要进行高时空分辨率的直接测量。在这篇综述中，我们讨论了调节膜纳米域形成和蛋白质功能的生化原理，范围从脂质纳米环境到皮质细胞骨架。我们还讨论了荧光显微镜的最新进展，这些进展使得在活细胞膜的纳米尺度上定量蛋白质组织和生化事件成为可能。
