title: Microtubule dynamics alter the interphase nucleus.
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 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.
authors.affiliation: Protein Section, Laboratory of Metabolism, National Cancer Institute, US National Institutes of Health, Bethesda, MD 20892, USA. gabi.gerlitz@gmail.com
authors.forename: Gabi
authors.initials: G
authors.lastname: Gerlitz
authors.forename: Orly
authors.initials: O
authors.lastname: Reiner
authors.forename: Michael
authors.initials: M
authors.lastname: Bustin
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D007399:Interphase / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D018715:Microscopy, Video; D022101:Microtubule-Organizing Center / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015739:Nocodazole / Q000494:pharmacology; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D055503:Protein Multimerization / Q000187:drug effects / Q000502:physiology; D050257:Tubulin Modulators / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D002843:Chromatin; D050257:Tubulin Modulators; D015739:Nocodazole