CRIF1 deficiency suppresses endothelial cell migration via upregulation of RhoGDI2

Nagar, Harsha; Kim, Seonhee; Lee, Ikjun; Choi, Si Hwan; Piao, Shuyu; Shong, Minho; Kim, Cuk-Seong

doi:10.1371/journal.pone.0256646

Cited by 6 publications

(6 citation statements)

References 62 publications

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“…Addition of exogenous AM2 led to increased expression of RAMP2, RAMP3, and AM2 in human umbilical vein endothelial cells (HUVECs). The authors posited that these findings could represents a mechanism by which AM2 compensates for CRIF1 deficiency ( Nagar et al, 2021 ). Clark and colleagues focused on endogenous CALCRL in human cardiomyocytes and HUVECs and demonstrated that CALCRL exhibits RAMP-dependent signaling bias using multiple cellular readouts ( Clark et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

et al. 2022

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G protein-coupled receptors (GPCRs) are known to interact with several other classes of integral membrane proteins that modulate their biology and pharmacology. However, the extent of these interactions and the mechanisms of their effects are not well understood. For example, one class of GPCR-interacting proteins, receptor activity-modifying proteins (RAMPs), comprise three related and ubiquitously expressed single-transmembrane span proteins. The RAMP family was discovered more than two decades ago, and since then GPCR–RAMP interactions and their functional consequences on receptor trafficking and ligand selectivity have been documented for several secretin (class B) GPCRs, most notably the calcitonin receptor-like receptor. Recent bioinformatics and multiplexed experimental studies suggest that GPCR–RAMP interactions might be much more widespread than previously anticipated. Recently, cryo-electron microscopy has provided high-resolution structures of GPCR–RAMP–ligand complexes, and drugs have been developed that target GPCR–RAMP complexes. In this review, we provide a summary of recent advances in techniques that allow the discovery of GPCR–RAMP interactions and their functional consequences and highlight prospects for future advances. We also provide an up-to-date list of reported GPCR–RAMP interactions based on a review of the current literature. Significance Statement Receptor activity-modifying proteins (RAMPs) have emerged as modulators of many aspects of G protein-coupled receptor (GPCR)biology and pharmacology. The application of new methodologies to study membrane protein–protein interactions suggests that RAMPs interact with many more GPCRs than had been previously known. These findings, especially when combined with structural studies of membrane protein complexes, have significant implications for advancing GPCR-targeted drug discovery and the understanding of GPCR pharmacology, biology, and regulation.

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Section: Introductionmentioning

confidence: 99%

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

et al. 2022

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“…Previous studies had demonstrated that the upregulated ARHGDIB could promote the macrophages in ltration and increase the production of ROS by regulating the activity of NADPH oxidase in phagocytes [33,34], indicating that the upregulated expression of ARHGDIB might aggravate the lung injury. Moreover, ARHGDIB could also inhibit the vascular endothelial cell migration and regulates vascular tone and other vascular functions [35]. The upregulated ARHGDIB could inhibit the expression of vascular endothelial growth factor (VEGF) which might suppress the regeneration of endothelial cells [36].…”

Section: Discussionmentioning

confidence: 99%

A Diagnostic Model for Sepsis-induced Acute Lung Injury Using a Consensus Machine Learning Approach

Zheng,

Wang,

Ling

et al. 2023

Preprint

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Background Sepsis-induced acute lung injury (ALI) is a heterogenous syndrome with high incidence and mortality. The diagnosis is often delayed which requires a chest imaging. Identifying diagnostic biomarkers may improve screening to identify septic patients at high risk of ALI earlier and provide the potential effective therapeutic drugs. Gene signatures obtained from peripheral blood have been shown to be dysregulated in sepsis and sepsis-induced ALI, which could provide additional noninvasive means for diagnosis. Machine learning algorithms are strong methods which can improve our ability to find relevant features in large and high-dimension data from gene expression profiles. The study aimed to develop a robust diagnostic model for the prediction of sepsis-induced ALI by using multiple machine learning algorithms, and validate the model for its predictive capability in external datasets.Methods The datasets were obtained from GEO and ArrayExpress databases. Following quality control and normalization, the datasets (GSE66890, GSE10474 and GSE32707) were merged as the training set, and four machine learning feature selection methods (Elastic net, svm, random forest and XGBoost) were applied to construct the diagnostic model. The other datasets were considered as the validation sets. Then, we explore the function of selected features and assess the correlation between selected features and immune cells. To further evaluated the performance and predictive value of diagnostic model, nomogram, Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) were constructed. Finally, the potential small molecular compounds interacting with selected features were explored from CTD database.Results The results of GSEA showed that immune response and metabolism might play an important role in the pathogenesis of sepsis-induced ALI. Then, 52 genes were identified as putative biomarkers by consensus feature selection from all four methods. Among them, 5 genes (ARHGDIB, ALDH1A1, TACR3, TREM1 and PI3) were selected by all methods and used to predict ALI diagnosis with high accuracy. The external datasets (E-MTAB-5273 and E-MTAB-5274) demonstrated that the diagnostic model have great accuracy with AUC value was 0.725 and 0.833, respectively. In addition, the nomogram, DCA and CIC showed that the diagnostic model had great performance and predictive value. Finally, the small molecular compounds (Curcumin, Tretinoin, Estradiol and Dexamethasone) were screened as the potential therapeutic agents for sepsis-induced ALI.Conclusion This consensus of multiple machine learning algorithms identified 5 genes (ARHGDIB, ALDH1A1, TACR3, TREM1 and PI3) that were able to distinguish ALI from septic patients. The diagnostic model could identify septic patients at high risk of ALI, and provide a promising therapeutic target for sepsis-induced ALI.

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“…Moreover, RhoGDIs can protect its interacting Rho GTPases from proteasomal degradation [ 22 ], demonstrating that RhoGDIs are not merely inhibitors for Rho GTPases but also have a key role in their regulation and signaling. Quite expectedly in view of these functions, both the RhoGDIs are involved in the regulation of multiple biological processes such as actin cytoskeletal organization, cell migration and immune response [ 23 , 24 , 25 , 26 ]. As mentioned previously, they are also implicated in many human cancers where they can either be upregulated or downregulated ( Table 1 ).…”

Section: Rhogdi1 and Rhogdi2: Similarities And Differencesmentioning

confidence: 99%

“…CRIF-1 (or CR6-interacting factor-1) is involved in mitochondrial functions and the regulation of cell growth. In human umbilical vein endothelial cells (HUVECs), RhoGDI2 is upregulated upon CRIF-1 silencing, which results in reduced cell migration possibly through the regulation of the activity of Rho GTPases [ 25 ]. In addition, RhoGDI2 has been shown to negatively regulate trophoblast migration via the inhibition of Rac1 activity.…”

Section: Regulatory Functions Of Rhogdi2mentioning

confidence: 99%

The Dual Function of RhoGDI2 in Immunity and Cancer

Tripathi

Colige

Deroanne

2023

IJMS

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RhoGDI2 is a guanine nucleotide dissociation inhibitor (GDI) specific for the Rho family of small GTPases. It is highly expressed in hematopoietic cells but is also present in a large array of other cell types. RhoGDI2 has been implicated in multiple human cancers and immunity regulation, where it can display a dual role. Despite its involvement in various biological processes, we still do not have a clear understanding of its mechanistic functions. This review sheds a light on the dual opposite role of RhoGDI2 in cancer, highlights its underappreciated role in immunity and proposes ways to explain its intricate regulatory functions.

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CRIF1 deficiency suppresses endothelial cell migration via upregulation of RhoGDI2

Cited by 6 publications

References 62 publications

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

A Diagnostic Model for Sepsis-induced Acute Lung Injury Using a Consensus Machine Learning Approach

The Dual Function of RhoGDI2 in Immunity and Cancer

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