Evolution of the Rho Family of Ras-Like GTPases in Eukaryotes

Boureux, Anthony; Vignal, Emmanuel; Faure, Sandrine; Fort, Philippe

doi:10.1093/molbev/msl145

Cited by 369 publications

(346 citation statements)

References 85 publications

(88 reference statements)

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“…3B). Consistent with Giardia being an early diverging eukaryote, its genome contains a single Rac homolog (28) and Rac is thought to be the founding member of the Rho family of small G proteins (29). To test for a conserved actin-signaling response in Giardia, we constructed a constitutive active Q74L giRac (equivalent to Q61L Rac1) (30).…”

Section: Resultsmentioning

confidence: 99%

An actin cytoskeleton with evolutionarily conserved functions in the absence of canonical actin-binding proteins

Paredez

Assaf

Sept

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

165

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Giardia intestinalis, a human intestinal parasite and member of what is perhaps the earliest-diverging eukaryotic lineage, contains the most divergent eukaryotic actin identified to date and is the first eukaryote known to lack all canonical actin-binding proteins (ABPs). We sought to investigate the properties and functions of the actin cytoskeleton in Giardia to determine whether Giardia actin (giActin) has reduced or conserved roles in core cellular processes. In vitro polymerization of giActin produced filaments, indicating that this divergent actin is a true filament-forming actin. We generated an anti-giActin antibody to localize giActin throughout the cell cycle. GiActin localized to the cortex, nuclei, internal axonemes, and formed C-shaped filaments along the anterior of the cell and a flagella-bundling helix. These structures were regulated with the cell cycle and in encysting cells giActin was recruited to the Golgi-like cyst wall processing vesicles. Knockdown of giActin demonstrated that giActin functions in cell morphogenesis, membrane trafficking, and cytokinesis. Additionally, Giardia contains a single G protein, giRac, which affects the Giardia actin cytoskeleton independently of known target ABPs. These results imply that there exist ancestral and perhaps conserved roles for actin in core cellular processes that are independent of canonical ABPs. Of medical significance, the divergent giActin cytoskeleton is essential and commonly used actin-disrupting drugs do not depolymerize giActin structures. Therefore, the giActin cytoskeleton is a promising drug target for treating giardiasis, as we predict drugs that interfere with the Giardia actin cytoskeleton will not affect the mammalian host. cytoskeleton evolution | actin protofilaments | MreB | endocytosis | Rac

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Section: Resultsmentioning

confidence: 99%

An actin cytoskeleton with evolutionarily conserved functions in the absence of canonical actin-binding proteins

Paredez

Assaf

Sept

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

165

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“…Rho GTPases play important regulatory roles in many intracellular activities including cell proliferation, differentiation, and apoptosis and carry out the molecular switching effects through transforming the styles between GTP-bound and GDP-bound (Boureux et al, 2007;Zhang et al, 2005). The Rho GTPases family is demonstrated to be the key regulators of actin cytoskeleton and cell junction (Heasman and Ridley, 2008).…”

Section: Discussionmentioning

confidence: 99%

Macrophage differentiation induced by PMA is mediated by activation of RhoA/ROCK signaling

Yang

Tang

et al. 2017

J. Toxicol. Sci.

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-In order to investigate the effects of RhoA/ROCK signaling in macrophage differentiation, we used 100 ng/mL PMA to induce macrophage differentiation from U937 cells in vitro. The observation of cell morphology and the expression of CD68 and SR-A were performed to confirm the differentiation induced by PMA. Western blot analysis showed that the expression of ROCK1 and ROCK2 and the phosphorylation of MYPT1 were significantly increased after PMA treatment. Pulldown assay showed that the activation of RhoA was obviously enhanced when U937 cells were treated with PMA. In order to further demonstrate whether RhoA/ROCK signaling could mediate the macrophage differentiation induced by PMA, we successfully suppressed the expression of RhoA, ROCK1 and ROCK2 by performing siRNA technology in U937 cells, respectively. The macrophage differentiation and the expression of CD68 and SR-A were significantly inhibited by the suppression of RhoA, ROCK1 or ROCK2 in PMA-induced U937 cells, indicating that the macrophage differentiation induced by PMA is associated with RhoA/ROCK signaling pathway. In addition, we pretreated U937 cells with Y27632 (ROCK inhibitor, 20 μM) for 30 min and then observed the macrophage differentiation induced by PMA. The result illustrated that Y27632 pretreatment obviously inhibited PMA-induced differentiation and the expression of CD68 and SR-A. In conclusion, the activation of RhoA/ROCK signaling is responsible for the macrophage differentiation induced by PMA.

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“…The activation of Rho is known to be mediated by three distinct functional classes of regulatory proteins, namely Rho guanine nucleotide exchange factors, Rho GTPase-activating proteins and RhoGDIs (Oleksy et al, 2006;Ridley, 2006;Boureux et al, 2007). By re-examining the CD146/ERM complex in A375 and SK-mel-28 cells, we found that CD146 was also coimunoprecipitated with RhoGDI1 (Figure 8a).…”

Section: Cd146/erm Complex Associates With Rhogdi1 and Promotes Rhoa mentioning

confidence: 96%

Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration

et al. 2011

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Tumor cell migration is a well-orchestrated multistep process that drives cancer development and metastasis. Previous data indicated that CD146 expression correlates with malignant progression and metastatic potential of human melanoma cells. However, the exact molecular mechanism of how CD146 promotes melanoma cell migration still remains poorly understood. Here, we report that CD146 physically interacts with actin-linking ezrin-radixin-moesin (ERM) proteins and recruits ERM proteins to cell protrusions, promoting the formation and elongation of microvilli. Moreover, CD146-promoted melanoma cell migration is linked to RhoA activation and ERM phosphorylation. CD146 recruits Rho guanine nucleotide dissociation inhibitory factors 1 (RhoGDI1) through ERM proteins and thus sequesters RhoGDI1 from RhoA, which leads to upregulated RhoA activity and increased melanoma cell motility. CD146-activated RhoA also promotes further ERM phosphorylation and activation through Rho-phosphatidylinositol-4-phosphate-5-kinase-phosphatidylinositol 4,5-biphosphate pathway, which reinforces CD146/ERM association. Thus, our results provide a mechanistic basis to understand the role of CD146 in regulating human melanoma cell motility.

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Evolution of the Rho Family of Ras-Like GTPases in Eukaryotes

Cited by 369 publications

References 85 publications

An actin cytoskeleton with evolutionarily conserved functions in the absence of canonical actin-binding proteins

An actin cytoskeleton with evolutionarily conserved functions in the absence of canonical actin-binding proteins

Macrophage differentiation induced by PMA is mediated by activation of RhoA/ROCK signaling

Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration

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