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.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Menon MB,Sawada A,Chaturvedi A,Mishra P,Schuster-Gossler K,Galla M,Schambach A,Gossler A,Förster R,Heuser M,Kotlyarov A,Kinoshita M,Gaestel Mdoi
10.1371/journal.pgen.1004558subject
Has Abstractpub_date
2014-08-14 00:00:00pages
e1004558issue
8eissn
1553-7390issn
1553-7404pii
PGENETICS-D-14-00693journal_volume
10pub_type
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