Microtubule dynamics alter the interphase nucleus


Microtubules are known to drive chromosome movements and to induce nuclear envelope breakdown during mitosis and meiosis. Here we show that microtubules can enforce nuclear envelope folding and alter the levels of nuclear envelope-associated heterochromatin during interphase, when the nuclear envelope is intact. Microtubule reassembly, after chemically induced depolymerization led to folding of the nuclear envelope and to a transient accumulation of condensed chromatin at the site nearest the microtubule organizing center (MTOC). This microtubule-dependent chromatin accumulation next to the MTOC is dependent on the composition of the nuclear lamina and the activity of the dynein motor protein. We suggest that forces originating from simultaneous polymerization of microtubule fibers deform the nuclear membrane and the underlying lamina. Whereas dynein motor complexes localized to the nuclear envelope that slide along the microtubules transfer forces and/or signals into the nucleus to induce chromatin reorganization and accumulation at the nuclear membrane folds. Thus, our study identified a molecular mechanism by which mechanical forces generated in the cytoplasm reshape the nuclear envelope, alter the intranuclear organization of chromatin, and affect the architecture of the interphase nucleus.

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We thank Trina A. Schroer (Department of Biology, Johns Hopkins University, Baltimore, MD, USA), Michael W. Davidson (National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, FL, USA) and Tom Misteli (NCI, NIH, MD, USA) for providing the plasmids, Valarie A. Barr (LCMB, NCI, NIH) for help with the confocal microscopy, and Kunio Nagashima and Christina M. Burks (Electron Microscope Laboratory, Advanced Technology Program, SAIC-Frederick, Inc. NCI, NIH, Frederick, MD, USA) for help with the TEM analysis. This work was supported by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute.

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Correspondence to Gabi Gerlitz.

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Supplementary Movie 1 Microtubule recovery induces nuclear alterations. GFP fused histone H1E (chromatin marker) and Cherry fused EB3 (centrosome marker) overexpressing cells were treated with nocodazole to induce microtubule depolymerization. Following the nocodazole removal, the cells were imaged every minute by the DeltaVision system package (Applied Precision, Issaquah, WA, USA) for 50 min. The speed of the movie that was generated by the Imaris software (Bitplane, Zurich, Switzerland) is 4 frames per second. 2 min passed between the nocodazole removal and the acquisition of the first frame, therefore 2 min should be added to the acquisition time shown at the bottom left side of the frame. The scale bar is 8 μm.(AVI 726 kb)

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Gerlitz, G., Reiner, O. & Bustin, M. Microtubule dynamics alter the interphase nucleus. Cell. Mol. Life Sci. 70, 1255–1268 (2013). https://doi.org/10.1007/s00018-012-1200-5

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  • Microtubules
  • Nuclear envelope
  • Lamins
  • Chromatin
  • Dynein