Abstract:
:The Rho GTPases RhoA and Rac1 function as master regulators of cytokinesis by controlling the actomyosin cytoskeleton. RhoA and Rac1 have to be respectively activated and inactivated at the division plane for cytokinesis to occur properly. The inactivation of Rac1 at the cleavage furrow is controlled by MgcRacGAP. However, the guanine-nucleotide exchange factor (GEF) that activates Rac1 during cell division remains unknown. Here, using a siRNA screening approach in HeLa cells, we identify Trio as a mitotic GEF of Rac1. We demonstrate that Trio controls Rac1 activation and subsequent F-actin remodeling in dividing cells. Moreover, Trio depletion specifically rescues the cytokinesis failure induced by MgcRacGAP depletion. Of importance, we demonstrate that this rescue is mediated by the Trio-Rac1 pathway, using GEF-dead mutants of Trio and a specific inhibitor of Rac1 activation by Trio. Overall this work identifies for the first time a GEF controlling Rac1 activation in dividing cells that counteracts MgcRacGAP function in cytokinesis.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Cannet A,Schmidt S,Delaval B,Debant Adoi
10.1091/mbc.E14-06-1153subject
Has Abstractpub_date
2014-12-15 00:00:00pages
4063-71issue
25eissn
1059-1524issn
1939-4586pii
mbc.E14-06-1153journal_volume
25pub_type
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