Leukemia-associated RhoGEF (LARG) is a novel RhoGEF in cytokinesis and required for the proper completion of abscission

Martz, Matthew; Grabocka, Elda; Beeharry, Neil; Yen, Tim J.; Wedegaertner, Philip

doi:10.1091/mbc.e12-07-0533

Cited by 24 publications

(25 citation statements)

References 58 publications

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“…Indeed, abscission failure can lead to cell death. 14,15 In addition, G1 mechanisms can couple or uncouple abscission onset to the cell cycle by a molecular switch unrelated to cell division. In fruit flies, for example, the number of germ cells in each Drosophila egg chamber is regulated by abscission inhibition during differentiation.…”

Section: Resultsmentioning

confidence: 99%

Cytokinetic abscission is an acute G1 event

et al. 2014

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Animal cell division ends with the cutting of the microtubule and membrane intercellular bridge connecting the 2 daughter cells. This process, known as cytokinetic abscission (abscission), is widely regarded as the last step of cytokinesis, i.e., the last step of the cell cycle. Major breakthroughs have been recently achieved, illuminating mechanistic aspects of abscission; however, the timing of abscission with respect to the mammalian cell cycle remains unclear. In this study, we carefully measured the onset and progression of abscission in dividing cells expressing a G1 reporter. We conclude that abscission commences long after cells enter the G1 phase. Affiliating abscission with G1 is beyond semantics since it essentially postulates that the last step of the cell cycle is regulated in, and probably by, the following cycle.

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Section: Resultsmentioning

confidence: 99%

Cytokinetic abscission is an acute G1 event

et al. 2014

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“…Two candidate GEFs are Ect2 and leukemia-associated RhoGEF (LARG), which also concentrate at the midbody ring. 154,155 The armadillo protein, p0071, is targeted to the midbody by the kinesin II KIF3b and once at the midbody ring associates with Ect2 and RhoA. 154,156 Upon binding it stimulates Ect2-mediated activation of RhoA.…”

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confidence: 99%

“…In contrast to depletion of Ect2 and GEF-H1, depletion of LARG causes cells to spend a prolonged period of time in abscission without affecting any other earlier stages of mitosis. 155 Thus, it is the only RhoA GEF whose function is specifically associated with the abscission stage of cytokinesis. Taken together, these studies provide tantalizing evidence to suggest that active RhoA plays a role during the abscission stage of cytokinesis.…”

mentioning

confidence: 99%

Rho GTPases as regulators of mitosis and cytokinesis in mammalian cells

Chircop

2014

Small GTPases

109

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“…Recently the RhoGEF LARG was shown to be required for the last step of cytokinesis, namely abscission (54). LARG localizes to the spindle poles and central spindle during mitosis, and to the midbody during cytokinesis.…”

Section: Rhogefs In Mitosis and Cytokinesismentioning

confidence: 99%

Controlling the switches: Rho GTPase regulation during animal cell mitosis

Zuo

Frost

2014

Cellular Signalling

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Animal cell division is a fundamental process that requires complex changes in cytoskeletal organization and function. Aberrant cell division often has disastrous consequences for the cell and can lead to cell senescence, neoplastic transformation or death. As important regulators of the actin cytoskeleton, Rho GTPases play major roles in regulating many aspects of mitosis and cytokinesis. These include centrosome duplication and separation, generation of cortical rigidity, microtubule-kinetochore stabilization, cleavage furrow formation, contractile ring formation and constriction, and abscission. The ability of Rho proteins to function as regulators of cell division depends on their ability to cycle between their active, GTP-bound and inactive, GDP-bound states. However, Rho proteins are inherently inefficient at fulfilling this cycle and require the actions of regulatory proteins that enhance GTP binding (RhoGEFs), stimulate GTPase activity (RhoGAPs), and sequester inactive Rho proteins in the cytosol (RhoGDIs). The roles of these regulatory proteins in controlling cell division are an area of active investigation. In this review we will delineate the current state of knowledge of how specific RhoGEFs, RhoGAPs and RhoGDIs control mitosis and cytokinesis, and highlight the mechanisms by which their functions are controlled.

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Leukemia-associated RhoGEF (LARG) is a novel RhoGEF in cytokinesis and required for the proper completion of abscission

Abstract: This study demonstrates a novel and unexpected role in cytokinesis for leukemia-associated RhoGEF (LARG). Depletion of LARG results in delayed abscission, and thus LARG is the first RhoGEF to be implicated in late cytokinesis.

Cited by 24 publications

References 58 publications

Cytokinetic abscission is an acute G1 event

Cytokinetic abscission is an acute G1 event

Rho GTPases as regulators of mitosis and cytokinesis in mammalian cells

Controlling the switches: Rho GTPase regulation during animal cell mitosis

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