Rho signaling: An historical and evolutionary perspective

Fort, Philippe

doi:10.1142/9789813228795_0001

Cited by 5 publications

(19 citation statements)

References 64 publications

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“…This confirms the well-documented roles of Rho, Rac, and Cdc42 in basic cellular metabolism and supports the data implicating RhoBTB2 in the control of proliferation, apoptosis, and membrane trafficking [ 74 , 75 ]. The time of emergence of Rnd and RhoUV is consistent with their roles in the acquisition of muscle and nerve cells, while the Cdc42 isoforms, RhoJQ and RhoDF, probably emerged at the time of origin of the vertebrate central nervous system [ 27 ]. A very important common characteristic of the entire Rho family is its high evolutionary dynamics, visible through the high incidence of gain and loss of its members in different animal lineages [ 14 ].…”

Section: The Rho Family Of Proteins Rho Gtpases In Non-bilateriamentioning

confidence: 99%

“…Boureux and coworkers [ 14 ] analyzed a draft genome of the sponge A. queenslandica (Reniera sp. JGI-2005) and identified one Rho protein, while Fort states [ 27 ] that the genome of this sponge has three Rho s.s. GTPases (stricto sensu, i.e., the ancestor to human RhoA-C). We have identified two Rho proteins (AqRho and AqRhoA) in the genome of A. queenslandica .…”

Section: The Rho Family Of Proteins Rho Gtpases In Non-bilateriamentioning

confidence: 99%

“…A single Cdc42 gene was found in the genome of the sponge A. queenslandica [ 14 , 27 ]. Analysis of the cDNA sequences (ESTs) from the marine sponge Suberites domuncula identified only one Cdc42 protein, named SdCdc42 [ 2 ].…”

Section: The Rho Family Of Proteins Rho Gtpases In Non-bilateriamentioning

confidence: 99%

“…Unicellular eukaryotes, fungi, and ancestral Metazoa contain only Rac, Cdc42, and RhoA GTPases ( Table 1 ) [ 15 ]. The fact that Rho genes are absent in sub-clades of Chlorophyta, Trypanosomatidae, Stramenopiles, and Alveolates can be explained by multiple independent gene-loss events [ 27 ]. The Rho family expanded in Metazoa (around 700 million years ago), probably as a result of duplication events and lateral gene transfers [ 15 ] ( Table 1 and Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

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Rho Family of Ras-Like GTPases in Early-Branching Animals

Beljan

Bosnar

Ćetković

2020

Cells

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Non-bilaterian animals consist of four phyla; Porifera, Cnidaria, Ctenophora, and Placozoa. These early-diverging animals are crucial for understanding the evolution of the entire animal lineage. The Rho family of proteins make up a major branch of the Ras superfamily of small GTPases, which function as key molecular switches that play important roles in converting and amplifying external signals into cellular responses. This review represents a compilation of the current knowledge on Rho-family GTPases in non-bilaterian animals, the available experimental data about their biochemical characteristics and functions, as well as original bioinformatics analysis, in order to gain a general insight into the evolutionary history of Rho-family GTPases in simple animals.

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Section: The Rho Family Of Proteins Rho Gtpases In Non-bilateriamentioning

confidence: 99%

Section: The Rho Family Of Proteins Rho Gtpases In Non-bilateriamentioning

confidence: 99%

Section: The Rho Family Of Proteins Rho Gtpases In Non-bilateriamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rho Family of Ras-Like GTPases in Early-Branching Animals

Beljan

Bosnar

Ćetković

2020

Cells

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“…Among atypical Rho GTPases, RhoU/Wrch‐1 was first identified as a gene target of the Wnt non‐canonical pathway [Tao et al., ]. RhoU forms with RhoV/Chp an evolutionary conserved sub‐family related to Rac and Cdc42 [Fort, ] and displays unusual features such as N‐terminal extension, atypical C‐terminal CAAX box and spontaneous activation [Saras et al., ; Berzat et al., ; Shutes et al., ]. In cultured cells, RhoU regulates focal adhesion formation and controls cell adhesion and migration [Chuang et al., ; Ory et al., ; Brazier et al., ], as well as tight junction formation and epithelial morphogenesis [Brady et al., ].…”

Section: Introductionmentioning

confidence: 99%

The atypical RhoU/Wrch1 Rho GTPase controls cell proliferation and apoptosis in the gut epithelium

Slaymi

Vignal

Crès

et al. 2019

Biology of the Cell

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Background. The mammalian gut epithelium displays among the highest rates of self-renewal, with a turnover time of less than 5 days. Renewal involves concerted proliferation at the bottom of the crypt, migration and differentiation along the crypt-villus axis and anoïkis/shedding in the luminal epithelium. Renewal is controlled by interplay between signalling pathways, among which canonical and non-canonical Wnt signals play prominent roles. Overall 92% of colon tumours show increased canonical Wnt signalling resulting from mutations, established as major driver steps towards carcinogenesis.Results. Here, we examined the physiological role of RhoU/Wrch1 in gut homeostasis. RhoU is an atypical Rho GTPase related to Cdc42/Rac1 and identified as a transcriptional target of non-canonical Wnt signalling. We found that RHOU expression is reduced in human colorectal tumour samples. We show that RhoU is mainly expressed in the differentiated compartment of the gut epithelium. Rhou specific invalidation in the mouse gut elicits cell hyperplasia and is associated in the colon with a highly disorganized luminal epithelium. Hyperplasia affects all cell types in the small intestine and colon and has a higher impact on goblet cells. Hyperplasia is associated with a reduction of apoptosis and an increased proliferation. RhoU knockdown in human DLD-1 colon cancer cells also elicits a higher growth index and reduces cell apoptosis. Last, loss of RhoU function in the mouse gut epithelium or in DLD-1 cells increases RhoA activity and the level of phosphorylated Myosin Light Chain-2, which may functionally link RhoU activity to apoptosis. Conclusion.RhoU is mostly expressed in the differentiated compartment of the gut. It plays a role in homeostasis as its specific invalidation elicits hyperplasia of all cell types. This mainly results from a reduction of apoptosis, through actomyosin-dependent mechanisms.Significance. RhoU negatively controls cell growth in the intestinal epithelium. Since its expression is sensitive to non-canonical Wnt signals and is reduced in colorectal tumours, downregulating RhoU may thus have an instrumental role in tumour progression.Additional supporting information may be found online in the Supporting Information section at the end of the article.

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A functional antagonism between RhoJ and Cdc42 regulates fibronectin remodelling during angiogenesis

Sundararaman

Mellor

2020

Small GTPases

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Angiogenesis is the formation of new blood vessels from pre-existing ones. Angiogenesis requires endothelial cells to change shape and polarity, as well as acquire the ability to directionally migrateprocesses that are classically regulated by the Rho family of GTPases. RhoJ (previously TCL) is an endothelium enriched Rho GTPase with a 78% amino acid similarity to the ubiquitously expressed Cdc42. In our recent publication, we demonstrate that α5β1 integrin co-traffics with RhoJ. RhoJ specifically represses the internalization of the active α5β1 conformer, leading to a reduced ability of endothelial cells to form fibronectin fibrils. Surprisingly, this function of RhoJ is in opposition to the role of Cdc42, a known driver of fibrillogenesis. Intriguingly, we discovered that the competition for limiting amounts of the shared effector, PAK3, could explain the ability of these two Rho GTPases to regulate fibrillogenesis in opposing directions. Consequently, RhoJ null mice show excessive fibronectin deposition around retinal vessels, possibly due to the unopposed action of Cdc42. Our work suggests that the functional antagonism between RhoJ and Cdc42 could restrict fibronectin remodelling to sites of active angiogenesis to form a provisional matrix for vessel growth. One correlate of our findings is that RhoJ dependent repression of fibronectin remodelling could be atheroprotective in quiescent vessels.

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Rho signaling: An historical and evolutionary perspective

Cited by 5 publications

References 64 publications

Rho Family of Ras-Like GTPases in Early-Branching Animals

Rho Family of Ras-Like GTPases in Early-Branching Animals

The atypical RhoU/Wrch1 Rho GTPase controls cell proliferation and apoptosis in the gut epithelium

A functional antagonism between RhoJ and Cdc42 regulates fibronectin remodelling during angiogenesis

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