Genetic Deletion of SEPT7 Reveals a Cell Type-Specific Role of Septins in Microtubule Destabilization for the Completion of Cytokinesis

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Genetic Deletion of SEPT7 Reveals a Cell Type-Specific Role of Septins in Microtubule Destabilization for the Completion of Cytokinesis

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Title: Genetic Deletion of SEPT7 Reveals a Cell Type-Specific Role of Septins in Microtubule Destabilization for the Completion of Cytokinesis
Author: Menon, Manoj B.; Sawada, Akihiro; Chaturvedi, Anuhar; Mishra, Pooja; Schuster-Gossler, Karin; Galla, Melanie; Schambach, Axel; Gossler, Achim; Förster, Reinhold; Heuser, Michael; Kotlyarov, Alexey; Kinoshita, Makoto; Gaestel, Matthias

Note: Order does not necessarily reflect citation order of authors.

Citation: Menon, M. B., A. Sawada, A. Chaturvedi, P. Mishra, K. Schuster-Gossler, M. Galla, A. Schambach, et al. 2014. “Genetic Deletion of SEPT7 Reveals a Cell Type-Specific Role of Septins in Microtubule Destabilization for the Completion of Cytokinesis.” PLoS Genetics 10 (8): e1004558. doi:10.1371/journal.pgen.1004558. http://dx.doi.org/10.1371/journal.pgen.1004558.
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Abstract: Cytokinesis terminates mitosis, resulting in separation of the two sister cells. Septins, a conserved family of GTP-binding cytoskeletal proteins, are an absolute requirement for cytokinesis in budding yeast. We demonstrate that septin-dependence of mammalian cytokinesis differs greatly between cell types: genetic loss of the pivotal septin subunit SEPT7 in vivo reveals that septins are indispensable for cytokinesis in fibroblasts, but expendable in cells of the hematopoietic system. SEPT7-deficient mouse embryos fail to gastrulate, and septin-deficient fibroblasts exhibit pleiotropic defects in the major cytokinetic machinery, including hyperacetylation/stabilization of microtubules and stalled midbody abscission, leading to constitutive multinucleation. We identified the microtubule depolymerizing protein stathmin as a key molecule aiding in septin-independent cytokinesis, demonstrated that stathmin supplementation is sufficient to override cytokinesis failure in SEPT7-null fibroblasts, and that knockdown of stathmin makes proliferation of a hematopoietic cell line sensitive to the septin inhibitor forchlorfenuron. Identification of septin-independent cytokinesis in the hematopoietic system could serve as a key to identify solid tumor-specific molecular targets for inhibition of cell proliferation.
Published Version: doi:10.1371/journal.pgen.1004558
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133155/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12785892
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