4.7 Article

Nucleoplasmin is a limiting component in the scaling of nuclear size with cytoplasmic volume

Journal

JOURNAL OF CELL BIOLOGY
Volume 218, Issue 12, Pages 4063-4078

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201902124

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Funding

  1. National Institutes of Health/National Institute of General Medical Sciences [R01GM113028, P20GM103432]
  2. American Cancer Society [RSG-15-035-01-DDC]
  3. National Science Foundation (Faculty CAREER program) [BBBE 1254608]

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How nuclear size is regulated relative to cell size is a fundamental cell biological question. Reductions in both cell and nuclear sizes during Xenopus laevis embryogenesis provide a robust scaling system to study mechanisms of nuclear size regulation. To test if the volume of embryonic cytoplasm is limiting for nuclear growth, we encapsulated gastrula-stage embryonic cytoplasm and nuclei in droplets of defined volume using microfluidics. Nuclei grew and reached new steady-state sizes as a function of cytoplasmic volume, supporting a limiting component mechanism of nuclear size control. Through biochemical fractionation, we identified the histone chaperone nucleoplasmin (Npm2) as a putative nuclear size effector. Cellular amounts of Npm2 decrease over development, and nuclear size was sensitive to Npm2 levels both in vitro and in vivo, affecting nuclear histone levels and chromatin organization. We propose that reductions in cell volume and the amounts of limiting components, such as Npm2, contribute to developmental nuclear size scaling.

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