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Nat Cell Biol 2009 Jan 01;111:71-7. doi: 10.1038/ncb1814.
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Regulation of cytokinesis by Rho GTPase flux.

In animal cells, cytokinesis is powered by a contractile ring of actin filaments (F-actin) and myosin-2. Formation of the contractile ring is dependent on the small GTPase RhoA, which is activated in a precise zone at the cell equator. It has long been assumed that cytokinesis and other Rho-dependent processes are controlled in a sequential manner, whereby Rho activation by guanine nucleotide exchange factors (GEFs) initiates a particular event, and Rho inactivation by GTPase activating proteins (GAPs) terminates that event. MgcRacGAP is a conserved cytokinesis regulator thought to be required only at the end of cytokinesis. Here we show that GAP activity of MgcRacGAP is necessary early during cytokinesis for the formation and maintenance of the Rho activity zone. Disruption of GAP activity by point mutation results in poorly focused Rho activity zones, whereas complete removal of the GAP domain results in unfocused zones that show lateral instability and/or rapid side-to-side oscillations. We propose that the GAP domain of MgcRacGAP has two unexpected roles throughout cytokinesis: first, it transiently anchors active Rho, and second, it promotes local Rho inactivation, resulting in the constant flux of Rho through the GTPase cycle.

PubMed ID: 19060892
PMC ID: PMC2677303
Article link: Nat Cell Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: actl6a ect2 racgap1 rho rho.2 rhoa
Morpholinos: racgap1 MO1 racgap1 MO2 racgap1 MO3

Article Images: [+] show captions
References [+] :
Ban, Human mitotic spindle-associated protein PRC1 inhibits MgcRacGAP activity toward Cdc42 during the metaphase. 2004, Pubmed