Genetic deletion of SEPT7 reveals a cell type-specific role of septins in microtubule destabilization for the completion of cytokinesis.

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 Genet

journal_title

PLoS genetics

authors

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 M

doi

10.1371/journal.pgen.1004558

subject

Has Abstract

pub_date

2014-08-14 00:00:00

pages

e1004558

issue

8

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-14-00693

journal_volume

10

pub_type

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