ARHGAP18, a GTPase-activating protein for RhoA, controls cell shape, spreading, and motility

Maeda, Masao; Hasegawa, Hitoki; Hyodo, Toshinori; Ito, Satoko; Asano, Eri; Yuang, Hong; Funasaka, Kohei; Shimokata, Kaoru; Hasegawa, Yoshinori; Hamaguchi, Michinari; Senga, Takeshi

doi:10.1091/mbc.e11-04-0364

Cited by 90 publications

(103 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Maeda et al previously reported that silencing of ARHGAP18 in epithelial cell lines induces a contracted phenotype with reduced spreading and pronounced stress fibers and focal adhesions. 26 Silencing of ARHGAP18 with the different siRNAs in EC did not result in gross morphological changes with the exception of siRNA-2, where significant cell elongation (Fig. S1B) was observed.…”

Section: Knockdown Of Arhgap18 Promotes Ec Migration and Sproutingmentioning

confidence: 83%

“…Interestingly ARHGAP18 displays RhoA and Rho1 (Drosophila RhoA homolog) GAP activity in epithelial cell lines and Drosophila S2 cells, respectively. 26,35 Such epithelial-endothelial differences in RhoGAP specificity have also been demonstrated in other RhoGAP family members, such as ARHGAP24/VasGAP/FliGAP. [36][37][38] RhoC belongs to the Rho subfamily and shares 92% sequence similarity but is functionally distinct as RhoC promotes, whereas RhoA inhibits tumor cell invasion and migration.…”

Section: E975002-8mentioning

confidence: 85%

“…ARHGAP18 exists as 2 isoforms, with the smaller isoform originating from a downstream start codon. 23,26 Knockdown of ARHGAP18 with siRNAs resulted in the reduced expression of both isoforms (Fig. S1A).…”

Section: Knockdown Of Arhgap18 Promotes Ec Migration and Sproutingmentioning

confidence: 98%

“…12,39 ARHGAP18 and the Drosophila ARHGAP18 ortholog, Conu, have been previously shown to translocate to the lamellipodia of migrating epithelial cells 26 and to the cortex of Drosophila epithelium, 35 respectively. We observed localization of ARHGAP18 to the junctions of sprouting and angiogenic EC.…”

Section: E975002-8mentioning

confidence: 99%

See 3 more Smart Citations

ARHGAP18: an endogenous inhibitor of angiogenesis, limiting tip formation and stabilizing junctions

et al. 2014

View full text Add to dashboard Cite

The formation of the vascular network requires a tightly controlled balance of pro-angiogenic and stabilizing signals. Perturbation of this balance can result in dysregulated blood vessel morphogenesis and drive pathologies including cancer. Here, we have identified a novel gene, ARHGAP18, as an endogenous negative regulator of angiogenesis, limiting pro-angiogenic signaling and promoting vascular stability. Loss of ARHGAP18 promotes EC hypersprouting during zebrafish and murine retinal vessel development and enhances tumor vascularization and growth. Endogenous ARHGAP18 acts specifically on RhoC and relocalizes to the angiogenic and destabilized EC junctions in a ROCK dependent manner, where it is important in reaffirming stable EC junctions and suppressing tip cell behavior, at least partially through regulation of tip cell genes, Dll4, Flk-1 and Flt-4. These findings highlight ARHGAP18 as a specific RhoGAP to fine tune vascular morphogenesis, limiting tip cell formation and promoting junctional integrity to stabilize the angiogenic architecture.

show abstract

Section: Knockdown Of Arhgap18 Promotes Ec Migration and Sproutingmentioning

confidence: 83%

Section: E975002-8mentioning

confidence: 85%

Section: Knockdown Of Arhgap18 Promotes Ec Migration and Sproutingmentioning

confidence: 98%

Section: E975002-8mentioning

confidence: 99%

See 2 more Smart Citations

ARHGAP18: an endogenous inhibitor of angiogenesis, limiting tip formation and stabilizing junctions

et al. 2014

View full text Add to dashboard Cite

show abstract

“…For instance, CTDSP1, an inversely correlated potential miR-183 target, has been shown to be involved in silencing neuronal genes through interaction with REST/NRSF, and CTDSP1 inactivation was found to promote neuronal differentiation of P19 stem cells (Yeo et al 2005). On the other hand, knockdown of ARHGAP18, a potential miR-183 target, enhanced stress fiber formation and induced rounding of cells (Maeda et al 2011). Likewise, potential miR-96 target genes included FARP1 that has been shown to promote dendritic growth of spinal motor neurons subtypes (Zhuang et al 2009) and LGI1 that has been implicated in the formation, differentiation, maintenance, and plasticity of neuronal synapses (Ko & Kim 2007).…”

Section: Mir183/96 Contribute To Pcc/pgl Tumorigenesis By Interferingmentioning

confidence: 99%

Integrative analysis of miRNA and mRNA expression profiles in pheochromocytoma and paraganglioma identifies genotype-specific markers and potentially regulated pathways

Cubas¹,

Leandro‐García²,

Schiavi³

et al. 2013

Endocrine-Related Cancer

View full text Add to dashboard Cite

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine neoplasias of neural crest origin that can be part of several inherited syndromes. Although their mRNA profiles are known to depend on genetic background, a number of questions related to tumor biology and clinical behavior remain unanswered. As microRNAs (miRNAs) are key players in the modulation of gene expression, their comprehensive analysis could resolve some of these issues. Through characterization of miRNA profiles in 69 frozen tumors with germline mutations in the genes SDHD, SDHB, VHL, RET, NF1, TMEM127, and MAX, we identified miRNA signatures specific to, as well as common among, the genetic groups of PCCs/PGLs. miRNA expression profiles were validated in an independent series of 30 composed of VHL-, SDHB-, SDHD-, and RET-related formalin-fixed paraffin-embedded PCC/PGL samples using quantitative real-time PCR. Upregulation of miR-210 in VHL-and SDHB-related PCCs/PGLs was verified, while miR-137 and miR-382 were confirmed as generally upregulated in PCCs/PGLs (except in MAX-related tumors). Also, we confirmed overexpression of miR-133b as VHL-specific miRNAs, miR-488 and miR-885-5p as RET-specific miRNAs, and miR-183 and miR-96 as SDHB-specific miRNAs. To determine the potential roles miRNAs play in PCC/PGL pathogenesis, we performed bioinformatic integration and pathway analysis using matched mRNA profiling data that indicated a common enrichment Finally, global proteomic analysis in SDHB and MAX tumors allowed us to determine that miRNA regulation occurs primarily through mRNA degradation in PCCs/PGLs, which partially confirmed our miRNA-mRNA integration results.

show abstract

Statistical profiling reveals correlations between the cell response to and the primary structure of Rho‐GAPs

2021

View full text Add to dashboard Cite

Rho‐GTPase‐activating proteins (Rho‐GAPs) are essential upstream regulators of the Rho family of GTPases. Currently, it remains unclear if the phenotypic change caused by perturbations to a Rho‐GAP is predictable from its amino acid sequence. Here we analyze the relationship between the morphological response of cells to the silencing of Rho‐GAPs and their primary structure. For all possible pairs of 57 different Rho‐GAPs expressed in MCF10A epithelial cells, the similarity in the Rho‐GAP silencing‐induced morphological change was quantified and compared to the similarity in the primary structure of the corresponding pairs. We found a distinct correlation between the morphological and sequence similarities in a specific group of RhoA‐targeting Rho‐GAPs. Thus, the family‐wide analysis revealed a common feature shared by the specific Rho‐GAPs.

show abstract

ARHGAP18, a GTPase-activating protein for RhoA, controls cell shape, spreading, and motility

Abstract: Using a library of siRNAs, we found that ARHGAP18 was essential for the organization of actin stress fibers and focal adhesion. ARHGAP18 is one of the crucial factors for the regulation of RhoA in order to control cell motility and spreading.

Cited by 90 publications

References 46 publications

ARHGAP18: an endogenous inhibitor of angiogenesis, limiting tip formation and stabilizing junctions

ARHGAP18: an endogenous inhibitor of angiogenesis, limiting tip formation and stabilizing junctions

Integrative analysis of miRNA and mRNA expression profiles in pheochromocytoma and paraganglioma identifies genotype-specific markers and potentially regulated pathways

Statistical profiling reveals correlations between the cell response to and the primary structure of Rho‐GAPs

Contact Info

Product

Resources

About