Interaction of RhoD and ZIP kinase modulates actin filament assembly and focal adhesion dynamics

Nehru, Vishal; Almeida, Francisca Nunes de; Aspenström, Pontus

doi:10.1016/j.bbrc.2013.02.046

Cited by 26 publications

(27 citation statements)

References 215 publications

(287 reference statements)

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“…When both proteins were depleted, early viral protein expression was not impaired but there was a substantial inhibition of cell contraction (Figures 2B and S2D). To explore whether additional signaling pathways also contribute to myosin-II activation, we treated cells with siRNA against myotonic dystrophy kinase-related Cdc42-binding kinases (MRCKα/β) and zipper-interacting protein kinase (ZIPK) (Nehru et al., 2013, Usui et al., 2014, Zhao and Manser, 2015). We found that WR-infected cells still contract in the absence of MRCKα/β and ZIPK (Figures 2C and 2D).…”

Section: Resultsmentioning

confidence: 99%

RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6

et al. 2017

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SummaryRhoA-mediated regulation of myosin-II activity in the actin cortex controls the ability of cells to contract and bleb during a variety of cellular processes, including cell migration and division. Cell contraction and blebbing also frequently occur as part of the cytopathic effect seen during many different viral infections. We now demonstrate that the vaccinia virus protein F11, which localizes to the plasma membrane, is required for ROCK-mediated cell contraction from 2 hr post infection. Curiously, F11-induced cell contraction is dependent on RhoC and not RhoA signaling to ROCK. Moreover, RhoC-driven cell contraction depends on the upstream inhibition of RhoD signaling by F11. This inhibition prevents RhoD from regulating its downstream effector Pak6, alleviating the suppression of RhoC by the kinase. Our observations with vaccinia have now demonstrated that RhoD recruits Pak6 to the plasma membrane to antagonize RhoC signaling during cell contraction and blebbing.

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Section: Resultsmentioning

confidence: 99%

RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6

et al. 2017

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“…DAPK3 is a protein kinase that modulates apoptosis-related signaling pathways (Wu et al, 2010) and, in interaction with RhoD , modulates actin filament assembly and focal adhesion reorganization (Nehru et al, 2013). S. aureus is known to induce apoptosis of host cells during host invasion, leading to a compromised host immune response (Haslinger-Löffler et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Genome wide association study of SNP-, gene-, and pathway-based approaches to identify genes influencing susceptibility to Staphylococcus aureus infections

Vasco

Carter

et al. 2014

Front. Genet.

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Background: We conducted a genome-wide association study (GWAS) to identify specific genetic variants that underlie susceptibility to diseases caused by Staphylococcus aureus in humans.Methods: Cases (n = 309) and controls (n = 2925) were genotyped at 508,921 single nucleotide polymorphisms (SNPs). Cases had at least one laboratory and clinician confirmed disease caused by S. aureus whereas controls did not. R-package (for SNP association), EIGENSOFT (to estimate and adjust for population stratification) and gene- (VEGAS) and pathway-based (DAVID, PANTHER, and Ingenuity Pathway Analysis) analyses were performed.Results: No SNP reached genome-wide significance. Four SNPs exceeded the p < 10−5 threshold including two (rs2455012 and rs7152530) reaching a p-value < 10−7. The nearby genes were PDE4B (rs2455012), TXNRD2 (rs3804047), VRK1 and BCL11B (rs7152530), and PNPLA5 (rs470093). The top two findings from the gene-based analysis were NMRK2 (pgene = 1.20E-05), which codes an integrin binding molecule (focal adhesion), and DAPK3 (pgene = 5.10E-05), a serine/threonine kinase (apoptosis and cytokinesis). The pathway analyses identified epithelial cell responses to mechanical and non-mechanical stress.Conclusion: We identified potential susceptibility genes for S. aureus diseases in this preliminary study but confirmation by other studies is needed. The observed associations could be relevant given the complexity of S. aureus as a pathogen and its ability to exploit multiple biological pathways to cause infections in humans.

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“…ZIPK not only regulates myosin activity, but it also regulates focal adhesion kinase (FAK) activity and cell adhesion. Importantly, constitutively active RhoD/ G26V can modulate this activity (Nehru et al, 2013a). The knock-down of RhoD results in the increased size of focal adhesions, which is one likely cause for the increased cell adhesion and decreased cell migration observed in cells that lack RhoD (Gad et al, 2012).…”

Section: Rhod and Rif Regulate Cytoskeletal Dynamics And Cell Migrationmentioning

confidence: 99%

Atypical Rho GTPases RhoD and Rif integrate cytoskeletal dynamics and membrane trafficking

Aspenström¹

2014

Biological Chemistry

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The Rho GTPases are essential regulators of basic cellular processes, including cell migration, cell contraction and cell division. Most studies still involve just the three canonical members, RhoA, Rac1 and Cdc42, although the Rho GTPases comprise at least 20 members. The aim of this review is to highlight some of the recent advances in our knowledge regarding the less-studied Rho members, with the focus on RhoD and Rif. The phenotypic alterations to cell behaviour that are triggered by RhoD and Rif suggest that they have unique impacts on cytoskeletal dynamics that distinguish them from the well-studied members of the Rho GTPases. In addition, RhoD has a role in the regulation of intracellular transport of vesicles. Taken together, the available data indicate that RhoD and Rif have functions as master regulators in the integration of cytoskeletal reorganisation and membrane trafficking.

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Interaction of RhoD and ZIP kinase modulates actin filament assembly and focal adhesion dynamics

Cited by 26 publications

References 215 publications

RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6

RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6

Genome wide association study of SNP-, gene-, and pathway-based approaches to identify genes influencing susceptibility to Staphylococcus aureus infections

Atypical Rho GTPases RhoD and Rif integrate cytoskeletal dynamics and membrane trafficking

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