期刊
EMBO REPORTS
卷 20, 期 6, 页码 -出版社
WILEY
DOI: 10.15252/embr.201847283
关键词
ELYS; nuclear pore complex; nuclear size; nucleocytoplasmic transport; nucleus
资金
- National Institutes of Health/National Institute of General Medical Sciences [R01GM113028]
- American Cancer Society [RSG-15-035-01-DDC]
- National Institutes of Health (NIH)
- National Cancer Institute
- Center for Cancer Research
- NATIONAL CANCER INSTITUTE [ZICBC011567] Funding Source: NIH RePORTER
How intracellular organelles acquire their characteristic sizes is a fundamental question in cell biology. Given stereotypical changes in nuclear size in cancer, it is important to understand the mechanisms that control nuclear size in human cells. Using a high-throughput imaging RNAi screen, we identify and mechanistically characterize ELYS, a nucleoporin required for post-mitotic nuclear pore complex (NPC) assembly, as a determinant of nuclear size in mammalian cells. ELYS knockdown results in small nuclei, reduced nuclear lamin B2 localization, lower NPC density, and decreased nuclear import. Increasing nuclear import by importin alpha overexpression rescues nuclear size and lamin B2 import, while inhibiting importin alpha/beta-mediated nuclear import decreases nuclear size. Conversely, ELYS overexpression increases nuclear size, enriches nuclear lamin B2 at the nuclear periphery, and elevates NPC density and nuclear import. Consistent with these observations, knockdown or inhibition of exportin 1 increases nuclear size. Thus, we identify ELYS as a novel positive effector of mammalian nuclear size and propose that nuclear size is sensitive to NPC density and nuclear import capacity.
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