RhoG-ELMO1-RAC1 is involved in phagocytosis suppressed by mono-butyl phthalate in TM4 cells

Gong, Pan; Chen, Shanshan; Zhang, Lulu; Hu, Yanhui; Gu, Aihua; Zhang, Jingshu; Wang, Yubang

doi:10.1007/s11356-018-3503-z

Cited by 7 publications

(5 citation statements)

References 59 publications

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“…Macrophages depleted in Elmo1 demonstrate an increase in the pH of phagolysosomes and a decrease in cathepsin B activity, which leads to better bacterial survival [36]. Moreover, the Elmo1 protein works unidirectionally with RhoG and Rac1, other phagocytosis-associated proteins involved in the RhoG-Elmo1-Rac1 cascade [37].…”

Section: Discussionmentioning

confidence: 99%

Proteome Profiling of PMJ2-R and Primary Peritoneal Macrophages

Русанов

Кожин

Tikhonova

et al. 2021

IJMS

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In vitro models are often used for studying macrophage functions, including the process of phagocytosis. The application of primary macrophages has limitations associated with the individual characteristics of animals, which can lead to insufficient standardization and higher variability of the obtained results. Immortalized cell lines do not have these disadvantages, but their responses to various signals can differ from those of the living organism. In the present study, a comparative proteomic analysis of immortalized PMJ2-R cell line and primary peritoneal macrophages isolated from C57BL/6 mice was performed. A total of 4005 proteins were identified, of which 797 were quantified. Obtained results indicate significant differences in the abundances of many proteins, including essential proteins associated with the process of phagocytosis, such as Elmo1, Gsn, Hspa8, Itgb1, Ncf2, Rac2, Rack1, Sirpa, Sod1, C3, and Msr1. These findings indicate that outcomes of studies utilizing PMJ2-R cells as a model of peritoneal macrophages should be carefully validated. All MS data are deposited in ProteomeXchange with the identifier PXD022133.

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Section: Discussionmentioning

confidence: 99%

Proteome Profiling of PMJ2-R and Primary Peritoneal Macrophages

Русанов

Кожин

Tikhonova

et al. 2021

IJMS

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“…Previous studies demonstrated that ELMO1 regulated cell migration by activating RAC proteins (Grimsley et al, 2004;Gong et al, 2018). There are three RAC genes, including RAC1, RAC2, and RAC3 in vertebrate.…”

Section: Constitutively Activated Rac Rescued the Neutrophil Motility Deficiency Of The Elmo1 Mutantmentioning

confidence: 99%

“…In addition to DOCK2, ELMO1 also interacts with DOCK180 to regulate cell migration (Grimsley et al, 2004). Through the interaction with DOCK proteins or RhoG and subsequent activation of the small GTPase such as RACs, ELMO1 involves in regulating lymphocyte migration or promoting cancer cells invasion (Katoh et al, 2003;Jiang et al, 2011;Capala et al, 2014;Stevenson et al, 2014;Gong et al, 2018;Park et al, 2020). Studies in mice and cell cultures have revealed reduced cell migration speeds due to Elmo1 deficiency.…”

Section: Introductionmentioning

confidence: 99%

Functional Verification of Novel ELMO1 Variants by Live Imaging in Zebrafish

Xue¹,

Wang²,

Wang³

et al. 2021

Front. Cell Dev. Biol.

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ELMO1 (Engulfment and Cell Motility1) is a gene involved in regulating cell motility through the ELMO1-DOCK2-RAC complex. Contrary to DOCK2 (Dedicator of Cytokinesis 2) deficiency, which has been reported to be associated with immunodeficiency diseases, variants of ELMO1 have been associated with autoimmune diseases, such as diabetes and rheumatoid arthritis (RA). To explore the function of ELMO1 in immune cells and to verify the functions of novel ELMO1 variants in vivo, we established a zebrafish elmo1 mutant model. Live imaging revealed that, similar to mammals, the motility of neutrophils and T-cells was largely attenuated in zebrafish mutants. Consequently, the response of neutrophils to injury or bacterial infection was significantly reduced in the mutants. Furthermore, the reduced mobility of neutrophils could be rescued by the expression of constitutively activated Rac proteins, suggesting that zebrafish elmo1 mutant functions via a conserved mechanism. With this mutant, three novel human ELMO1 variants were transiently and specifically expressed in zebrafish neutrophils. Two variants, p.E90K (c.268G>A) and p.D194G (c.581A>G), could efficiently recover the motility defect of neutrophils in the elmo1 mutant; however, the p.R354X (c.1060C>T) variant failed to rescue the mutant. Based on those results, we identified that zebrafish elmo1 plays conserved roles in cell motility, similar to higher vertebrates. Using the transient-expression assay, zebrafish elmo1 mutants could serve as an effective model for human variant verification in vivo.

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“…Rho Guanine nucleotide exchange factor 16 (ARHGEF16) codifies an ELMO1 interacting protein responsible to promote the clearance of apoptotic cells in a RhoG-dependent and Dock1-independent manner [66]. The relationship between ARHGEF16 and fertility has yet to be described in the literature, such as by Elliott et al (2010) and Gong et al (2018). Interestingly, ELMO1 knockout mice presented multinucleated giant cells, uncleared apoptotic germ cells, and decreased sperm output in Sertoli cells owing to the phagocytic deficiency [67,68].…”

Section: Differentially Co-expressed Modules and The Identification Of Functional Candidate Genesmentioning

confidence: 99%

“…The relationship between ARHGEF16 and fertility has yet to be described in the literature, such as by Elliott et al (2010) and Gong et al (2018). Interestingly, ELMO1 knockout mice presented multinucleated giant cells, uncleared apoptotic germ cells, and decreased sperm output in Sertoli cells owing to the phagocytic deficiency [67,68]. However, there is no link between Elmo1 and female fertility currently described.…”

Section: Differentially Co-expressed Modules and The Identification Of Functional Candidate Genesmentioning

confidence: 99%

Weighted Gene Correlation Network Meta-Analysis Reveals Functional Candidate Genes Associated with High- and Sub-Fertile Reproductive Performance in Beef Cattle

Fonseca

Suárez-Vega

Cánovas

2020

Genes

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Improved reproductive efficiency could lead to economic benefits for the beef industry, once the intensive selection pressure has led to a decreased fertility. However, several factors limit our understanding of fertility traits, including genetic differences between populations and statistical limitations. In the present study, the RNA-sequencing data from uterine samples of high-fertile (HF) and sub-fertile (SF) animals was integrated using co-expression network meta-analysis, weighted gene correlation network analysis, identification of upstream regulators, variant calling, and network topology approaches. Using this pipeline, top hub-genes harboring fixed variants (HF × SF) were identified in differentially co-expressed gene modules (DcoExp). The functional prioritization analysis identified the genes with highest potential to be key-regulators of the DcoExp modules between HF and SF animals. Consequently, 32 functional candidate genes (10 upstream regulators and 22 top hub-genes of DcoExp modules) were identified. These genes were associated with the regulation of relevant biological processes for fertility, such as embryonic development, germ cell proliferation, and ovarian hormone regulation. Additionally, 100 candidate variants (single nucleotide polymorphisms (SNPs) and insertions and deletions (INDELs)) were identified within those genes. In the long-term, the results obtained here may help to reduce the frequency of subfertility in beef herds, reducing the associated economic losses caused by this condition.

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RhoG-ELMO1-RAC1 is involved in phagocytosis suppressed by mono-butyl phthalate in TM4 cells

Cited by 7 publications

References 59 publications

Proteome Profiling of PMJ2-R and Primary Peritoneal Macrophages

Proteome Profiling of PMJ2-R and Primary Peritoneal Macrophages

Functional Verification of Novel ELMO1 Variants by Live Imaging in Zebrafish

Weighted Gene Correlation Network Meta-Analysis Reveals Functional Candidate Genes Associated with High- and Sub-Fertile Reproductive Performance in Beef Cattle

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