Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.
Cell. 2019 Feb 7;176(4):805-815.e8. doi: 10.1016/j.cell.2018.12.001. Epub 2019 Jan 10.
Early embryogenesis is accompanied by reductive cell divisions requiring that subcellular structures adapt to a range of cell sizes. The interphase nucleus and mitotic spindle scale with cell size through both physical and biochemical mechanisms, but control systems that coordinately scale intracellular structures are unknown. We show that the nuclear transport receptor importin α is modified by palmitoylation, which targets it to the plasma membrane and modulates its binding to nuclear localization signal (NLS)-containing proteins that regulate nuclear and spindle size in Xenopus egg extracts. Reconstitution of importin α targeting to the outer boundary of extract droplets mimicking cell-like compartments recapitulated scaling relationships observed during embryogenesis, which were altered by inhibitors that shift levels of importin α palmitoylation. Modulation of importin α palmitoylation in human cells similarly affected nuclear and spindle size. These experiments identify importin α as a conserved surface area-to-volume sensor that scales intracellular structures to cell size.
早期胚胎发生伴随着还原细胞分裂，这需要亚细胞结构适应一系列细胞大小。有丝分裂间期核和纺锤体通过物理和生化机制与细胞大小成比例缩放，但协调细胞内结构比例缩放的控制系统尚不清楚。我们发现核转运受体 importin α 被棕榈酰化修饰，使其靶向质膜，并调节其与核定位信号（NLS）-含有蛋白质的结合，这些蛋白质调节 Xenopus 卵提取物中的核和纺锤体大小。模拟细胞样隔室的外边界的 importin α 靶向重建再现了胚胎发生过程中观察到的比例关系，而通过改变 importin α 棕榈酰化水平的抑制剂改变了这些比例关系。在人细胞中调节 importin α 棕榈酰化同样影响了核和纺锤体的大小。这些实验确定了 importin α 作为一种保守的表面积到体积传感器，可将细胞内结构按细胞大小进行缩放。
