Importin α Partitioning to the Plasma Membrane Regulates Intracellular Scaling

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 alpha 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 alpha 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 alpha palmitoylation. Modulation of importin a palmitoylation in human cells similarly affected nuclear and spindle size. These experiments identify importin a as a conserved surface area-to-volume sensor that scales intracellular structures to cell size.