Rho-kinase Contributes to Sustained RhoA Activation through Phosphorylation of p190A RhoGAP

Mori, Kazutaka; Amano, Mutsuki; Takefuji, Mikito; Kato, Katsuhiro; Morita, Yasuhiro; Nishioka, Tomoki; Matsuura, Yoshiharu; Murohara, Toyoaki; Kaibuchi, Kozo

doi:10.1074/jbc.m806853200

Cited by 57 publications

(45 citation statements)

References 40 publications

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“…Phosphorylation and dephosphorylation have been shown to regulate GAP function in a number of different eukaryotic cells (Sopko et al 2007;Zheng et al 2007;Toure et al 2008;McAvoy et al 2009;Mori et al 2009;Wolfe et al 2009). Therefore, we hypothesize that PP2A-Pab1 inhibition of Spg1 is more likely to operate indirectly, perhaps through activating dephosphorylation of the Cdc16-Byr4 two-component GAP.…”

Section: Resultsmentioning

confidence: 99%

Antagonistic Roles of PP2A-Pab1 and Etd1 in the Control of Cytokinesis in Fission Yeast

et al. 2010

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In Schizosaccharomyces pombe, Etd1 is a positive regulator of the septation initiation network (SIN), a conserved GTPase-regulated kinase cascade that triggers cytokinesis. Here we show that a mutation in the pab1 gene, which encodes the B-regulatory subunit of the protein phosphatase 2A (PP2A), suppresses mutations in the etd1 gene. Etd1 is required for the function of the GTPase Spg1, a key regulator of SIN signaling. Interestingly, the loss of Pab1 function restored the activity of Spg1 in Etd1-deficient cells. This result suggests that PP2A-Pab1-mediated dephosphorylation inhibits Spg1, thus antagonizing Etd1 function. The loss of pab1 function also rescues the lethality of mutants of other genes in the SIN cascade such as mob1, sid1, and cdc11. Two-hybrid assays indicate that Pab1 physically interacts with Mob1, Sid1, Sid2, and Cdc11, suggesting that the phosphatase 2A B-subunit is a component of the SIN complex. Together, our results indicate that PP2A-Pab1 plays a novel role in cytokinesis, regulating SIN activity at different levels. Pab1 is also required to activate polarized cell growth. Thus, PP2A-Pab1 may be involved in coordinating polar growth and cytokinesis.

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Section: Resultsmentioning

confidence: 99%

Antagonistic Roles of PP2A-Pab1 and Etd1 in the Control of Cytokinesis in Fission Yeast

et al. 2010

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“…Interestingly, RhoA activity is higher in the growth cones of minor neurites of polarized neurons than in the growing axon (Gonzalez-Billault et al, 2012). Rho kinase phosphorylates and inactivates p190 RhoGAP, a member of GTPase-activating proteins (GAPs; negative regulators of Rho family proteins), leading to sustained RhoA activation (Mori et al, 2009). Thus, the continuous activation of RhoA/Rho kinase might be required not only for axon specification but also for the maintenance of neuronal polarity by preventing the formation of multiple axons.…”

Section: Rho Family Proteins In Neuronal Polaritymentioning

confidence: 99%

Neuronal polarization

et al. 2015

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Neurons are highly polarized cells with structurally and functionally distinct processes called axons and dendrites. This polarization underlies the directional flow of information in the central nervous system, so the establishment and maintenance of neuronal polarization is crucial for correct development and function. Great progress in our understanding of how neurons establish their polarity has been made through the use of cultured hippocampal neurons, while recent technological advances have enabled in vivo analysis of axon specification and elongation. This short review and accompanying poster highlight recent advances in this fascinating field, with an emphasis on the signaling mechanisms underlying axon and dendrite specification in vitro and in vivo.

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“…p190 GAP is inhibited by phosphorylation and activated by PP2A-mediated dephosphorylation (Mori et al 2009). Similar results have been recently shown for Rho GAP activation in a number of different eukaryotic cells (Sopko et al 2007;Zheng et al 2007;Toure et al 2008;McAvoy et al 2009;Mori et al 2009;Wolfe et al 2009). Since rga5D and rga1D null mutants suppress lethality of Etd1-depleted cells, inhibition of Rho1 by PP2A-Pab1 could be exerted through dephosphorylation and activation of these Rho1 GAPs (see model in Figure 8).…”

Section: Rho1 Inhibition By Pp2a-pab1mentioning

confidence: 99%

Feedback Regulation of SIN by Etd1 and Rho1 in Fission Yeast

et al. 2014

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In fission yeast, the septation initiation network (SIN) is thought to promote cytokinesis by downstream activation of Rho1, a conserved GTPase that controls cell growth and division. Here we show that Etd1 and PP2A-Pab1, antagonistic regulators of SIN, are Rho1 regulators. Our genetic and biochemical studies indicate that a C-terminal region of Etd1 may activate Rho1 by directly binding it, whereas an N-terminal domain confers its ability to localize at the growing tips and the division site where Rho1 functions. In opposition to Etd1, our results indicate that PP2A-Pab1 inhibits Rho1. The SIN cascade is upstream-regulated by the Spg1 GTPase. In the absence of Etd1, activity of Spg1 drops down prematurely, thereby inactivating SIN. Interestingly, we find that ectopic activation of Rho1 restores Spg1 activity in Etd1-depleted cells. By using a cytokinesis block strategy, we show that Rho1 is essential to feedbackactivate Spg1 during actomyosin ring constriction. Therefore, activation of Spg1 by Rho1, which in turn is regulated by Etd1, uncovers a novel feedback loop mechanism that ensures SIN activity while cytokinesis is progressing.F ISSION yeast cells grow by elongating at their cell ends before dividing by forming a medially placed division septum during cytokinesis. New-born cells initiate growth in a monopolar manner from the old cell end that existed before division. During G2, cells initiate growth from the new end in a process known as NETO (new end take-off). These cells then grow in a bipolar mode until mitosis, when they stop growth and initiate cell division by septation (Mitchison and Nurse 1985;Hayles and Nurse 2001). Both polar growth and septation require proper cell membrane and cell-wall synthesis to ensure cell integrity. In Schizosaccharomyces pombe, the cell wall is composed of b-glucan, a-glucan, and mannoproteins. Synthesis of the major cell wall and primary septum polymer, 1,3-b-glucan, requires the activity of Drc1/Cps1/Bgs1 1,3-b-glucan synthase, which in turn is regulated by the guanosine triphosphate (GTP)-binding protein Rho1 (Garcia et al. 2006;Cortes et al. 2007). As with all GTPases, Rho1 acts as a binary switch, cycling between inactive GDP-bound and active GTPbound conformational states (Yang et al. 2003). This transition is controlled by three types of proteins: GEFs (guanine exchange factors), which catalyze the exchange of GDP for GTP, rendering the protein active; GAPs (GTPase activating proteins), which enhance nucleotide hydrolysis, inactivating the GTPase; and guanine nucleotide dissociation inhibitors, which appear to block spontaneous activation (Garcia et al. 2006).Upon the onset of mitosis, growth ceases at the cell ends and is re-established in the middle of the cell, where the actomyosin ring forms. At the end of mitosis, once the two sets of chromosomes have segregated, actomyosin ring constriction and septum formation is triggered by the septation initiation network (SIN) from the spindle pole body (SPB) (Krapp et al. 2004;Wolfe and Gould 2005). The nucl...

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Rho-kinase Contributes to Sustained RhoA Activation through Phosphorylation of p190A RhoGAP

Cited by 57 publications

References 40 publications

Antagonistic Roles of PP2A-Pab1 and Etd1 in the Control of Cytokinesis in Fission Yeast

Antagonistic Roles of PP2A-Pab1 and Etd1 in the Control of Cytokinesis in Fission Yeast

Neuronal polarization

Feedback Regulation of SIN by Etd1 and Rho1 in Fission Yeast

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