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Upon nuclear envelope (NE) fragmentation in the prometaphase, the nuclear and cytosolic proteomes mix and must be redefined to reinstate homeostasis. Here, by using a molecular GFP ladder, we show that in early mitosis, condensed chromatin excludes cytosolic proteins. When the NE reforms tightly around condensed chromatin in late mitosis, large GFP multimers are automatically excluded from the nucleus. This can be circumvented by limiting DNA condensation with Q15, a condensin II inhibitor. Soluble small and other nuclear localization sequence (NLS)-targeted proteins then swiftly enter the expanding nuclear space. We then examined proteasomes, which are located in the cytoplasm and nucleus. A significant fraction of 20S proteasomes is imported by the importin IPO5 within 20 min of reformation of the nucleus, after which import comes to an abrupt halt. This suggests that maintaining the nuclear-cytosol distribution after mitosis requires chromatin condensation to exclude cytosolic material from the nuclear space, and specialized machineries for nuclear import of large protein complexes, such as the proteasome., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

When cell surface receptors engage their cognate ligands in the extracellular space, they become competent to transmit potent signals to the inside of the cell, thereby instigating growth, differentiation, motility and many other processes. In order to control these signals, activated receptors are endocytosed and thoroughly curated by the endosomal network of intracellular vesicles and proteolytic organelles. In this Review, we follow the epidermal growth factor (EGF) receptor (EGFR) from ligand engagement, through its voyage on endosomes and, ultimately, to its destruction in the lysosome. We focus on the spatial and temporal considerations underlying the molecular decisions that govern this complex journey and discuss how additional cellular organelles - particularly the ER - play active roles in the regulation of receptor lifespan. In summarizing the functions of relevant molecules on the endosomes and the ER, we cover the order of molecular events in receptor activation, trafficking and downregulation, and provide an overview of how signaling is controlled at the interface between these organelles., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)