CYK-4 regulates Rac, but not Rho, during cytokinesis

Abstract

The roles of the Rho-family GAP CYK-4 and small GTPase Rac during cytokinesis are examined in Caenorhabditis elegans embryos. CYK-4 opposes Rac (and potentially Cdc42) activity during cytokinesis. There is no evidence that CYK-4 is upstream of Rho activity or that Rac disruption is a general suppressor of cytokinesis failure.

Polar relaxation by dynein-mediated removal of cortical myosin II

“…4a-c). The point mutation of this temperature sensitive allele lies in the GAP domain of CYK-4 (Canman et al, 2008;Davies et al, 2014) and prevents the equatorial stimulation since the GAP domain plays a role in equatorial stimulation by inactivation of Rac (Canman et al, 2008;Zhuravlev et al, 2017) or by activation of Rho via the RhoGEF ECT-2 (Loria et al, 2012;Tse et al, 2012;Zhang and Glotzer, 2015). Importantly, unlike other methods used to perturb the centralspindlin/central spindle-dependent pathway, this allele, at the restrictive temperature (25 °C), achieves this without affecting the formation and maintenance of the central spindle or the localization of centralspindlin to the spindle midzone (Canman et al, 2008).…”

Mitotic Cell Division in Caenorhabditis elegans

“…Work in Xenopus epithelia has also revealed a dramatic increase in active Rac when the CYK-4 ortholog is inhibited (Breznau et al 2015), providing evidence that CYK-4 orthologs do inactivate Rac in vivo in some contexts. In C. elegans, inhibition of the Rac1 GTPase CED-10 can suppress cytokinesis defects resulting from cyk-4 inhibition (Canman et al 2008;Zhuravlev et al 2017). The idea that the GAP activity of CYK-4 could contribute to cytokinesis by inactivating Rac originated with the isolation of recessive, TS, separation-offunction mutations in cyk-4 that do not disrupt central spindle assembly or centralspindlin localization, but nevertheless result in the same compromised furrow ingression observed after more complete reduction of CYK-4 function.…”

“…The idea that the GAP activity of CYK-4 could contribute to cytokinesis by inactivating Rac originated with the isolation of recessive, TS, separation-offunction mutations in cyk-4 that do not disrupt central spindle assembly or centralspindlin localization, but nevertheless result in the same compromised furrow ingression observed after more complete reduction of CYK-4 function. The cytokinesis defect caused by these special cyk-4 alleles can be partially rescued by reducing CED-10/Rac1 or the Rac1 target Arp2/3 (Canman et al 2008;Zhuravlev et al 2017). Because CED-10/Rac1 promotes the Arp2/3-dependent assembly of branched cortical microfilaments, downregulation of CED-10/Rac1 is proposed to decrease or prevent branched microfilament assembly such that the compromised cytokinesis furrow can ingress to completion.…”

Nine unanswered questions about cytokinesis

“…Second, during cytokinesis cells inhibit the GTPase Rac, which may reduce cortical stiffness from branched actin filaments. The centralspindlin RacGAP promotes the hydrolysis of GTP bound to Rac ( Zhuravlev et al, 2017 ), and the Rac GEF Trio is inhibited ( Cannet et al, 2014 ). Third, Aurora B kinase in the chromosomal passenger complex antagonizes global inhibition of centralspindlin oligomerization by PAR-5/14-3-3 ( Basant et al, 2015 ) but is only required before the ring starts to assemble ( Davies et al, 2014 ).…”

“… Signaling pathways controlling the assembly of contractile rings in animals. This schematic is based on figures from Glotzer (2016) and Zhuravlev et al (2017) . It is a synthesis of information from experiments on nematode zygotes and vertebrate cells.…”