GTPase Domain Driven Dimerization of SEPT7 is Dispensable for the Critical Role of Septins in Fibroblast Cytokinesis

Overview

Journal Sci Rep

Specialty Science

Date 2016 Jan 29

PMID 26818767

Citations 15

Authors

Megha Abbey

Cosima Hakim

Roopsee Anand

Juri Lafera

Axel Schambach

Andreas Kispert

Manuel H Taft

Volkhard Kaever

Alexey Kotlyarov

Matthias Gaestel

Manoj B Menon

Affiliations

Soon will be listed here.

Abstract

Septin 7 (SEPT7) has been described to be essential for successful completion of cytokinesis in mouse fibroblasts, and Sept7-deficiency in fibroblasts constitutively results in multinucleated cells which stop proliferation. Using Sept7(flox/flox)fibroblasts we generated a cellular system, where the cytokinetic defects of Cre-mediated deletion of the Sept7 gene can be rescued by ectopically expressed doxycycline-inducible wild type SEPT7. Using this system, we analyzed the ability of SEPT7-mutants with alterations in their GTPase domain-dependent dimerization to prevent multinucleation and rescue proliferation. Although biochemical analysis of the mutants demonstrates differences in homo- and/or hetero-polymerization, in GTP-binding and/or GTPase activities, all analyzed mutants were able to rescue the cytokinesis phenotype of Sept7(flox/flox)fibroblasts associated with Cre-mediated deletion of endogenous Sept7. These findings indicate that the ability of septins to assemble into well-defined SEPT7-dimerization dependent native filaments is dispensable for cytokinesis in fibroblasts and opens the way to search for other mechanisms of the involvement of SEPT7 in cytokinesis.

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