Microtubule dynamics alter the interphase nucleus
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Cellular and Molecular Life Sciences
RESEARCH ARTICLE
Microtubule dynamics alter the interphase nucleus Gabi Gerlitz • Orly Reiner • Michael Bustin
Received: 31 August 2012 / Revised: 9 October 2012 / Accepted: 15 October 2012 / Published online: 2 November 2012 Ó Springer Basel (outside the USA) 2012
Abstract 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 Electronic supplementary material The online version of this article (doi:10.1007/s00018-012-1200-5) contains supplementary material, which is available to authorized users. G. Gerlitz M. Bustin Protein Section, Laboratory of Metabolism, National Cancer Institute, US National Institutes of Health, Bethesda, MD 20892, USA G. Gerlitz O. Reiner Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel G. Gerlitz (&) Department of Molecular Biology, Ariel University Center of Samaria, 44837 Ariel, Israel e-mail: [email protected]; [email protected]
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. Keywords Microtubules Nuclear envelope Lamins Chromatin Dynein
Introduction Microtubules and their interacting proteins play a major role in shaping the architecture of the genome during mitosis and meiosis. At the onset of both mitosis and meiosis, nuclear envelope breakdown is driven by stretching forces generated by the dynein motor proteins that are anchored to it while sliding along microtubules towards the spindle poles [1–3]. Following nuclear envelope breakdown, the microtubules and their motor proteins kinesin and dynein drive the migration of the chromosomes and their attachment to the spindle [4, 5]. Likewise, the generation of the ‘‘meiotic bouquet’’, a cluster of chromosomes that are linked to the nuclear envelope through their telomeres during early stages of meiosis, has been shown to be dependent on microtubules
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