A newly identified Rab-GDI paralogue has a role in neural development in amphibia

Nazlamova, Liliya; Noble, Anna; Schubert, Frank; McGeehan, J.E.; Myers, Fiona A.; Guille, Matthew; Scarlett, Garry

doi:10.1016/j.gene.2016.11.013

Cited by 5 publications

(3 citation statements)

References 29 publications

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“…Herein, we have demonstrated that Rab4A is a modulator of endocytic volume because Rab4A overexpression leads to increased endosomal size in both MCF10A and MDA-MB-231, whereas knockdown of Rab4A results in increased endosomal size in MCF10A but not in MDA-MB-231 cells. Previously, similar results have been shown in other cell types (59)(60)(61), suggesting that precise control of Rab4 expression regulates EE volume in a cell-specific manner. Considering that Rab4 has been shown to be involved in both membrane fusion and fission events (58,62), changes in Rab4 expression could result in increased EE size.…”

Section: Discussionsupporting

confidence: 82%

Complex Rab4-Mediated Regulation of Endosomal Size and EGFR Activation

Tubbesing

Ward

Abini-Agbomson

et al. 2020

Molecular Cancer Research

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Early sorting endosomes are responsible for the trafficking and function of transferrin receptor (TfR) and EGFR. These receptors play important roles in iron uptake and signaling and are critical for breast cancer development. However, the role of morphology, receptor composition, and signaling of early endosomes in breast cancer remains poorly understood. A novel population of enlarged early endosomes was identified in breast cancer cells and tumor xenografts but not in noncancerous MCF10A cells. Quantitative analysis of endosomal morphology, cargo sorting, EGFR activation, and Rab GTPase regulation was performed using superresolution and confocal microscopy followed by 3D rendering. MDA-MB-231 breast cancer cells have fewer, but larger EEA1positive early endosomes compared with MCF10A cells. Live-cell imaging indicated dysregulated cargo sorting, because EGF and Tf traffic together via enlarged endosomes in MDA-MB-231, but not in MCF10A. Large EEA1-positive MDA-MB-231 endosomes exhibited prolonged and increased EGF-induced activation of EGFR upon phosphorylation at tyrosine-1068 (EGFR-p1068). Rab4A overexpression in MCF10A cells produced EEA1-positive enlarged endosomes that displayed prolonged and amplified EGF-induced EGFR-p1068 activation. Knockdown of Rab4A lead to increased endosomal size in MCF10A, but not in MDA-MB-231 cells. Nevertheless, Rab4A knockdown resulted in enhanced EGF-induced activation of EGFR-p1068 in MDA-MB-231 as well as downstream signaling in MCF10A cells. Altogether, this extensive characterization of early endosomes in breast cancer cells has identified a Rab4-modulated enlarged early endosomal compartment as the site of prolonged and increased EGFR activation.Implications: Enlarged early endosomes play a Rab4-modulated role in regulation of EGFR activation in breast cancer cells.

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Section: Discussionsupporting

confidence: 82%

Complex Rab4-Mediated Regulation of Endosomal Size and EGFR Activation

Tubbesing

Ward

Abini-Agbomson

et al. 2020

Molecular Cancer Research

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“…In the current work, we focused on Rab-GDI2 function because it contributes to vesicle shuttling by regulating the activity of RAB GTPases. Rab-GDI2 regulates the GDP/GTP exchange of RAB proteins by inhibiting the dissociation of GDP and the subsequent binding of GTP 51 . A latest report shows that Rab-GDI2 is a target of paclitaxel that affects the tumorigenesis of prostate cancer 52 .…”

Section: Discussionmentioning

confidence: 99%

Vesicle-mediated transport-related genes predict the prognosis and immune microenvironment in hepatocellular carcinoma

Ye,

Wang,

Yuan

et al. 2024

J. Cancer

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Background : Liver hepatocellular carcinoma (LIHC) is one of the leading causes of cancer-related death. The prognostic outcomes of advanced LIHC patients are poor. Hence, reliable prognostic biomarkers for LIHC are urgently needed. Methods : Data for vesicle-mediated transport-related genes (VMTRGs) were profiled from 338 LIHC and 50 normal tissue samples downloaded from The Cancer Genome Atlas (TCGA). Univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct and optimize the prognostic risk model. Five GEO datasets were used to validate the risk model. The roles of the differentially expressed genes (DEGs) were investigated via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses. Differences in immune cell infiltration between the high- and low-risk groups were evaluated using five algorithms. The “pRRophetic” was used to calculate the anticancer drug sensitivity of the two groups. Transwell and wound healing assays were performed to assess the role of GDP dissociation inhibitor 2 (GDI2) on LIHC cells. Results : A total of 166 prognosis-associated VMTRGs were identified, and VMTRGs-based risk model was constructed for the prognosis of LIHC patients. Four VMTRGs (GDI2, DYNC1LI1, KIF2C, and RAB32) constitute the principal components of the risk model associated with the clinical outcomes of LIHC. Tumor stage and risk score were extracted as the main prognostic indicators for LIHC patients. The VMTRGs-based risk model was significantly associated with immune responses and high expression of immune checkpoint molecules. High-risk patients were less sensitive to most chemotherapeutic drugs but benefited from immunotherapies. In vitro cellular assays revealed that GDI2 significantly promoted the growth and migration of LIHC cells. Conclusions : A VMTRGs-based risk model was constructed to predict the prognosis of LIHC patients effectively. This risk model was closely associated with the immune infiltration microenvironment. The four key VMTRGs are powerful prognostic biomarkers and therapeutic targets for LIHC.

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“…The vast majority is maintained in the cytosol through GDIs ( Garcia-Mata et al, 2011 ). As opposed to GEFs and GAPs, GDIs exist in a limited number with only three members (RhoGDI-1, -2, -3, RabGDIα, -β, -3) identified so far ( Nazlamova et al, 2017 ; Muller and Goody, 2018 ; Ahmad Mokhtar et al, 2021 ).…”

Section: Rho and Rab Family Small Gtpasesmentioning

confidence: 99%

Rho and Rab Family Small GTPases in the Regulation of Membrane Polarity in Epithelial Cells

Ebnet

Gerke

2022

Front. Cell Dev. Biol.

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Membrane polarity, defined as the asymmetric distribution of lipids and proteins in the plasma membrane, is a critical prerequisite for the development of multicellular tissues, such as epithelia and endothelia. Membrane polarity is regulated by polarized trafficking of membrane components to specific membrane domains and requires the presence of intramembrane diffusion barriers that prevent the intermixing of asymmetrically distributed membrane components. This intramembrane diffusion barrier is localized at the tight junctions (TJs) in these cells. Both the formation of cell-cell junctions and the polarized traffic of membrane proteins and lipids are regulated by Rho and Rab family small GTPases. In this review article, we will summarize the recent developments in the regulation of apico-basal membrane polarity by polarized membrane traffic and the formation of the intramembrane diffusion barrier in epithelial cells with a particular focus on the role of Rho and Rab family small GTPases.

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A newly identified Rab-GDI paralogue has a role in neural development in amphibia

Cited by 5 publications

References 29 publications

Complex Rab4-Mediated Regulation of Endosomal Size and EGFR Activation

Complex Rab4-Mediated Regulation of Endosomal Size and EGFR Activation

Vesicle-mediated transport-related genes predict the prognosis and immune microenvironment in hepatocellular carcinoma

Rho and Rab Family Small GTPases in the Regulation of Membrane Polarity in Epithelial Cells

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