Cdc42 GTPase activating proteins Rga4 and Rga6 coordinate septum synthesis and membrane trafficking at the division plane during cytokinesis

Campbell, Bethany F; Hercyk, Brian S.; Williams, Ashlei R.; Miguel, Emalyn S San; Young, Haylee G.; Das, Maitreyi

doi:10.1101/2021.12.14.472679

Cited by 1 publication

(1 citation statement)

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“…During growth in fission yeast, Cdc42 is restricted to growing tips primarily via the activity of its GAP Rga4 (Das et al, 2007; Rich-Robinson et al, 2021). At the onset of ring constriction during cytokinesis, Cdc42 GAPs also localize to the division site (Campbell et al, 2021; Rich-Robinson et al, 2021). These GAPs may establish distinct zones that are devoid of active Cdc42 where Rho1 activation can occur to finally allow septum formation.…”

Section: Discussionmentioning

confidence: 99%

Cdc42 prevents precocious Rho1 activation during cytokinesis in a Pak1-dependent manner

Onwubiko

Koory

Pokharel

et al. 2022

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Cytokinesis consists of a series of coordinated multi-step events that partition a dividing cell. Accurate regulation of cytokinesis is essential for proliferation and genome integrity. In fission yeast, these coordinated events ensure that the actomyosin ring and septum start ingressing only after chromosome segregation. How cytokinetic events are coordinated is unclear. The GTPase Cdc42 is required for the delivery of certain cell wall-building enzymes while the GTPase Rho1 is required for activation of these enzymes. Here we show that Cdc42 prevents early Rho1 activation during cytokinesis. Using a Rho-probe, we report that Rho1 is activated in late anaphase, just before the onset of ring constriction, even though, the primary Rho1 activators Rgf1 and Rgf3 localize to the division site in early anaphase. We find that loss of Cdc42 activation enables precocious Rho1 activation in early anaphase. Furthermore, this inhibition of Rho1 activation is dependent on the downstream Cdc42 effector Pak1 kinase. Disrupting pak1 function resulted in early Rho1 activation accompanied by precocious septum deposition and ring constriction. We provide functional and genetic evidence which indicates that Pak1 regulates Rho1 activation likely via the regulation of its GEF Rgf1. Our work proposes a mechanism of regulation of Rho1 by active Cdc42 to coordinate timely septum formation and cytokinesis fidelity.

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