Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Curriculum in Bioinformatics and Computational Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nat Cell Biol. 2022 Apr;24(4):461-470. doi: 10.1038/s41556-022-00882-3. Epub 2022 Apr 11.
Biomolecular condensates organize biochemistry, yet little is known about how cells control the position and scale of these structures. In cells, condensates often appear as relatively small assemblies that do not coarsen into a single droplet despite their propensity to fuse. Here, we report that ribonucleoprotein condensates of the glutamine-rich protein Whi3 interact with the endoplasmic reticulum, which prompted us to examine how membrane association controls condensate size. Reconstitution revealed that membrane recruitment promotes Whi3 condensation under physiological conditions. These assemblies rapidly arrest, resembling size distributions seen in cells. The temporal ordering of molecular interactions and the slow diffusion of membrane-bound complexes can limit condensate size. Our experiments reveal a trade-off between locally enhanced protein concentration at membranes, which favours condensation, and an accompanying reduction in diffusion, which restricts coarsening. Given that many condensates bind endomembranes, we predict that the biophysical properties of lipid bilayers are key for controlling condensate sizes throughout the cell.
生物分子凝聚物组织生物化学，但对于细胞如何控制这些结构的位置和规模知之甚少。在细胞中，凝聚物通常表现为相对较小的组装体，尽管它们有融合的倾向，但不会粗化为单个液滴。在这里，我们报告富含谷氨酰胺的蛋白质 Whi3 的核糖核蛋白凝聚物与内质网相互作用，这促使我们研究膜结合如何控制凝聚物的大小。重建实验表明，在生理条件下，膜募集促进了 Whi3 的凝聚。这些组装体迅速停止，类似于在细胞中观察到的大小分布。分子相互作用的时间顺序和膜结合复合物的缓慢扩散可以限制凝聚物的大小。我们的实验揭示了在膜处局部增强蛋白质浓度有利于凝聚，以及伴随而来的扩散减少限制了粗化之间的权衡。鉴于许多凝聚物与内膜结合，我们预测脂质双层的物理特性是控制整个细胞中凝聚物大小的关键。
