Rho GEFs in endothelial junctions

Ngok, Siu P.; Anastasiadis, Panos Z.

doi:10.4161/tisb.27132

Cited by 10 publications

(5 citation statements)

References 60 publications

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“…This requires a tight control of the spatial and temporal activation pattern of each of the GTPases involved. The molecular mechanisms controlling these processes are still not well characterized, but several RhoGEFs and RhoGAPs are identified to modulate this process ( Aijaz et al, 2005 ; Sousa et al, 2005 ; Terry et al, 2011 ; Holeiter et al, 2012 ; Nishimura et al, 2012 ; Ratheesh et al, 2012 ; Tripathi et al, 2012 ; Ngok and Anastasiadis, 2013 ; Zebda et al, 2013 ; Breznau et al, 2015 ). Silencing the expression of these GEFs and GAPs alters junction integrity or interferes with contractility, suggesting that multiple GEFs and GAPs regulate different functions at cell junctions ( Ratheesh et al, 2013 ; Ngok et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility

Awadia

Huq

Arnold

et al. 2019

Journal of Cell Biology

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The canonical Scribble polarity complex is implicated in regulation of epithelial junctions and apical polarity. Here, we show that SGEF, a RhoG-specific GEF, forms a ternary complex with Scribble and Dlg1, two members of the Scribble complex. SGEF targets to apical junctions in a Scribble-dependent fashion and functions in the regulation of actomyosin-based contractility and barrier function at tight junctions as well as E-cadherin–mediated formation of adherens junctions. Surprisingly, SGEF does not control the establishment of polarity. However, in 3D cysts, SGEF regulates the formation of a single open lumen. Interestingly, SGEF’s nucleotide exchange activity regulates the formation and maintenance of adherens junctions, and in cysts the number of lumens formed, whereas SGEF’s scaffolding activity is critical for regulation of actomyosin contractility and lumen opening. We propose that SGEF plays a key role in coordinating junctional assembly and actomyosin contractility by bringing together Scribble and Dlg1 and targeting RhoG activation to cell–cell junctions.

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Section: Discussionmentioning

confidence: 99%

SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility

Awadia

Huq

Arnold

et al. 2019

Journal of Cell Biology

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“…59 The small GTPases of Rho family and Rap GTPases control the endothelial barrier function by regulating the spatial organization and contractility of junction-associated actin cytoskeleton. [60][61][62] RhoA can activate various effector proteins in endothelial cells that may affect junction integrity. ROCK is one of the key regulators of linear junction disassembly.…”

Section: Regulation Of Ajs By Rho and Rap Gtpasesmentioning

confidence: 99%

Cadherin-mediated cell-cell interactions in normal and cancer cells

2017

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Adherens junctions (AJs) are molecular complexes that mediate cell-cell adhesive interactions and play pivotal roles in maintenance of tissue organization in adult organisms and at various stages of development. AJs consist of cadherin adhesion receptors, providing homophilic ligation with cadherins on adjacent cells, and members of the catenin protein family: p120, β- and α-catenin. α-catenin's linkage with the actin cytoskeleton defines the linear or punctate organization of AJs in different cell types. Myosin II-dependent tension drives vinculin recruitment by α-catenin and stabilizes the linkage of the cadherin/catenin complex to F-actin. Neoplastic transformation leads to prominent changes in the organization, regulation and stability of AJs. Epithelial-mesenchymal transition (EMT) whereby epithelial cells lose stable cell-cell adhesion, and reorganize their cytoskeleton to acquire migratory activity, plays the central role in cancer cell invasion and metastasis. Recent data demonstrated that a partial EMT resulting in a hybrid epithelial/mesenchymal phenotype with retention of E-cadherin is essential for cancer cell dissemination. E-cadherin and E-cadherin-based AJs are required for collective invasion and migration, survival in circulation, and metastatic outgrowth.

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“…This suggests that plekhg5 plays a more fundamental role than shroom3 in the assembly of the apical actomyosin network. As both Shroom3 and Plekhg5 are apically localized and can activate ROCK via either direct binding to ROCK or Rho activation ( Ngok and Anastasiadis, 2013 ; Das et al. , 2014 ; Mack and Georgiou, 2014 ), the difference in their function in regulating apical actin accumulation may reflect other distinct partners and downstream effectors of these two factors.…”

Section: Discussionmentioning

confidence: 99%

The RhoGEF protein Plekhg5 regulates medioapical and junctional actomyosin dynamics of apical constriction during Xenopus gastrulation

Baldwin

Popov

Keller

et al. 2023

MBoC

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Apical constriction results in apical surface reduction in epithelial cells and is a widely used mechanism for epithelial morphogenesis. Both medioapical and junctional actomyosin remodeling are involved in apical constriction, but the deployment of medial versus junctional actomyosin and their genetic regulation in vertebrate embryonic developmental has not been fully described. In this study, we investigate actomyosin dynamics and their regulation by the RhoGEF protein Plekhg5 in Xenopus bottle cells. Using live imaging and quantitative image analysis, we show that bottle cells assume different shapes, with rounding bottle cells constricting earlier in small clusters followed by fusiform bottle cells forming between the clusters. Both medioapical and junctional actomyosin signals increase as surface area decreases, though correlation of apical constriction with medioapical actomyosin localization appears stronger. F-actin bundles perpendicular to the apical surface form in constricted cells, which may correspond to microvilli previously observed in the apical membrane. Knockdown of plekhg5 disrupts medioapical and junctional actomyosin activity and apical constriction but does not affect initial F-actin dynamics. Taken together, our study reveals distinct cell morphologies, uncovers actomyosin behaviors, and demonstrates the crucial role of a RhoGEF protein in controlling actomyosin dynamics during apical constriction of bottle cells in Xenopus gastrulation. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

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Rho GEFs in endothelial junctions

Cited by 10 publications

References 60 publications

SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility

SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility

Cadherin-mediated cell-cell interactions in normal and cancer cells

The RhoGEF protein Plekhg5 regulates medioapical and junctional actomyosin dynamics of apical constriction during Xenopus gastrulation

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