Polo-Like Kinase Cdc5 Controls the Local Activation of Rho1 to Promote Cytokinesis

Abstract

The links between the cell cycle machinery and the cytoskeletal proteins controlling cytokinesis are poorly understood. The small guanine nucleotide triphosphate (GTP)-binding protein RhoA stimulates type II myosin contractility and formin-dependent assembly of the cytokinetic actin contractile ring. We found that budding yeast Polo-like kinase Cdc5 controls the targeting and activation of Rho1 (RhoA) at the division site via Rho1 guanine nucleotide exchange factors. This role of Cdc5 (Polo-like kinase) in regulating Rho1 is likely to be relevant to cytokinesis and asymmetric cell division in other organisms.

α-Synuclein disrupts stress signaling by inhibiting polo-like kinase Cdc5/Plk2

“…Sakchaisri and colleagues discovered that Cdc5, which localizes to the bud neck (21), phosphorylates Tus1 and that phospho-Tus1 concentrates at the bud neck where it activates Rho1 to trigger cytokinesis (14). These latter authors proposed that Cdc5 also controls the global level of GTP-Rho1 by its ability to phosphorylate and, thus, activate or inactivate Rho1 GEFs or Rho1 GAPs, respectively.…”

“…For this assay, BY4741 cdc15-2 cells, which are arrested in anaphase at 37°C (14), were used. Lysates from cdc15-2 cells expressing Tus1-myc and αS or αS(Δ2-10) were incubated with the various purified GST constructs, and then after several washing steps samples were subjected to SDS/PAGE followed by Western blotting with an antimyc antibody (Fig.…”

“…Recent studies have shown that in neurons, Plk2 regulates the activity of two small guanosine triphosphatases (GTPases), Ras and Rap, by phosphorylating their activators (GEFs, guanine nucleotide exchange factors) and inactivators (GAPs, GTPase-activating proteins) (12,13). In yeast, Cdc5 also regulates the activity of the small GTPase Rho1 by phosphorylating its GEFs (Tus1 and Rom2) and GAP (Sac7) (14).…”

Polo Kinase and Cytokinesis Initiation in Mammalian Cells: Harnessing the Awesome Power of Chemical Genetics

“…Strikingly, such cells executed anaphase and exited mitosis, but failed to initiate cytokinesis. Consistent with the function of Cdc5 (the Plk ortholog in yeast), 27 Plk1 activity was required for equatorial recruitment of the RhoA GTPase, the key switch for contractile ring assembly and furrow ingression during cytokinesis. 28 In addition, Plk1 was required to recruit itself and the RhoGEF (Rho guanine nucleotide exchange factor) Ect2 to the central spindle, whereas the Ect2 binding partner, CYK-4 (a GAP or GTPase activating protein for RhoA) was properly recruited despite Plk1 inhibition.…”

Cytokinesis in Metazoa and Fungi

“…Other important events in ring assembly are temporally regulated by a polo kinase ortholog, Cdc5. Cdc5 promotes accumulation of the RhoGEF Tus1 at the bud neck shortly after anaphase (Yoshida et al 2006). Tus1, in turn, activates Rho1, inducing local recruitment of the formin Bni1, which nucleates assembly of the actin filaments in the contractile ring (Fig.…”