The vertebrate epithelial apical junctional complex: Dynamic interplay between Rho GTPase activity and cell polarization processes

Díaz-Díaz, Covadonga; Baonza, Gabriel; Martı́n-Belmonte, Fernando

doi:10.1016/j.bbamem.2020.183398

Cited by 15 publications

(11 citation statements)

References 181 publications

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“…Moreover, spatiotemporal insight into how the polarity network functions is limited, and little is known about the mechanisms and structural principles that control the underlying PPIs. Likewise, although the polarity proteins are central to the regulation of the HIPPO pathway [224,225,241] and Rho GTPase signaling [1,[29][30][31][32][33][34], our understanding of how cell polarity development is integrated with cytoskeletal dynamics and cell growth and survival to orchestrate epithelial tissue morphogenesis is incomplete, and many questions remain unanswered (Box 2).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…We focus on the mammalian polarity proteins but provide reference to invertebrate systems, most notably Drosophila, whenever useful and informative (see Table 1 for protein and gene names in Drosophila and mammals). We refer the reader to excellent recent reviews on related topics, including the composition and regulation of epithelial cell junctions [25][26][27][28], the role of small GTPases [1,[29][30][31][32][33][34] and the Scribble module [35,36] in epithelial polarity development, and the functions of the polarity proteins in epithelial lumen formation [37,38].…”

Section: Introductionmentioning

confidence: 99%

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New insights into the organization and regulation of the apical polarity network in mammalian epithelial cells

et al. 2021

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Cell polarity is a fundamental property of most animal cells and is critical during development and for most cell and tissue functions. Epithelial cells are organized into apical and basolateral compartments, and this intrinsic cellular asymmetry is essential for all functions that are carried out by epithelial tissue. The establishment of a polarized epithelial phenotype is orchestrated by major rearrangements of the cell cytoskeleton, polarized membrane trafficking, the formation and maturation of epithelial cell junctions, cell signaling pathways, and the generation of cortical phospholipid asymmetry. These processes need to be coordinated precisely in time and space and integrated with physical and chemical signals from the environment, failure of which leads to severe developmental disorders and various human diseases. At the heart of this regulatory network are the evolutionarily conserved polarity modules Par, Crumbs, and Scribble, whose components engage in complex cooperative and antagonistic interactions to compartmentalize and functionalize the epithelial cell cortex and to control the spatiotemporal activity of downstream polarity effectors. In this review, we will discuss recent insights into the organization and regulation of the mammalian Par and Crumbs modules and outline a hypothetical framework of how these proteins orchestrate epithelial polarity development, HIPPO signaling, and actomyosin activity at the apical–lateral border.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New insights into the organization and regulation of the apical polarity network in mammalian epithelial cells

et al. 2021

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“…Studies have shown that Cdc42, a member of the Rho GTPase family, which together with other family members, including RhoA, Rac1, Rac2, RhoH, RohD/F, RhoU/V affect cell movement, endocytosis, cell morphology and cell cycle progression through their effects on actin cytoskeletal organization [ 111 , 112 , 113 , 114 , 115 ]. More important, Cdc42, together with Rac1 and RhoA, affect the dynamics of filopodia, lamellipodia and stress fibers, namely their assembly (formation), disassembly and maintenance [ 116 , 117 , 118 , 119 , 120 ]. The concerted efforts of these GTPases thus confer cell migration in fibroblasts, macrophages, and other locomotive cells under physiological conditions, including cancer cells during tumorigenesis, making GTPases one of the prime targets of cancer treatment.…”

Section: Fak (Focal Adhesion Kinase) and Small Gtpase Cdc42mentioning

confidence: 99%

Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models

Wang

et al. 2022

Cells

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Emerging evidence has shown that cell-cell interactions between testicular cells, in particular at the Sertoli cell-cell and Sertoli-germ cell interface, are crucial to support spermatogenesis. The unique ultrastructures that support cell-cell interactions in the testis are the basal ES (ectoplasmic specialization) and the apical ES. The basal ES is found between adjacent Sertoli cells near the basement membrane that also constitute the blood-testis barrier (BTB). The apical ES is restrictively expressed at the Sertoli-spermatid contact site in the apical (adluminal) compartment of the seminiferous epithelium. These ultrastructures are present in both rodent and human testes, but the majority of studies found in the literature were done in rodent testes. As such, our discussion herein, unless otherwise specified, is focused on studies in testes of adult rats. Studies have shown that the testicular cell-cell interactions crucial to support spermatogenesis are mediated through distinctive signaling proteins and pathways, most notably involving FAK, Akt1/2 and Cdc42 GTPase. Thus, manipulation of some of these signaling proteins, such as FAK, through the use of phosphomimetic mutants for overexpression in Sertoli cell epithelium in vitro or in the testis in vivo, making FAK either constitutively active or inactive, we can modify the outcome of spermatogenesis. For instance, using the toxicant-induced Sertoli cell or testis injury in rats as study models, we can either block or rescue toxicant-induced infertility through overexpression of p-FAK-Y397 or p-FAK-Y407 (and their mutants), including the use of specific activator(s) of the involved signaling proteins against pAkt1/2. These findings thus illustrate that a potential therapeutic approach can be developed to manage toxicant-induced male reproductive dysfunction. In this review, we critically evaluate these recent findings, highlighting the direction for future investigations by bringing the laboratory-based research through a translation path to clinical investigations.

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“…The small GTPases, Rho, Rac and Cdc42 are versatile regulators of the cytoskeleton, which regulate epithelial cell polarity and morphogenesis. [68][69][70][71] When bound to GTP, they modulate the activity of multiple effector proteins, amongst them several protein kinases.…”

Section: Actin Regulating Proteins As Targets Of Rosmentioning

confidence: 99%

Reactive oxygen species (ROS) constitute an additional player in regulating epithelial development

Hebbar

Knust

2021

BioEssays

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Reactive oxygen species (ROS) are highly reactive molecules produced in cells. So far, they have mostly been connected to diseases and pathological conditions. More recent results revealed a somewhat unexpected role of ROS in control of developmental processes. In this review, we elaborate on ROS in development, focussing on their connection to epithelial tissue morphogenesis. After briefly summarising unique characteristics of epithelial cells, we present some characteristic features of ROS species, their production and targets, with a focus on proteins important for epithelial development and function. Finally, we provide examples of regulation of epithelial morphogenesis by ROS, and also of developmental genes that regulate the overall redox status. We conclude by discussing future avenues of research that will further elucidate ROS regulation in epithelial development.

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The vertebrate epithelial apical junctional complex: Dynamic interplay between Rho GTPase activity and cell polarization processes

Cited by 15 publications

References 181 publications

New insights into the organization and regulation of the apical polarity network in mammalian epithelial cells

New insights into the organization and regulation of the apical polarity network in mammalian epithelial cells

Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction—Lesson from the Toxicant/Pharmaceutical Models

Reactive oxygen species (ROS) constitute an additional player in regulating epithelial development

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