scholarly journals The transmembrane protein Crb2a regulates cardiomyocyte apicobasal polarity and adhesion in zebrafish

2018 ◽  
Author(s):  
Vanesa Jiménez-Amilburu ◽  
Didier Y.R. Stainier
Keyword(s):  
Cell Adhesion ◽  
Cardiac Development ◽  
Transmembrane Protein ◽  
Critical Role ◽  
Apicobasal Polarity ◽  
Junctional Protein ◽  
Summary Statement ◽  
Erbb2 Signaling ◽  
Complex Display ◽  
Cell Cell

AbstractTissue morphogenesis requires changes in cell-cell adhesion as well as in cell shape and polarity. Cardiac trabeculation is a morphogenetic process essential to form a functional ventricular wall. Here we show that zebrafish hearts lacking Crb2a, a component of the Crumbs polarity complex, display compact wall integrity defects and fail to form trabeculae. Crb2a localization is very dynamic, at a time when other cardiomyocyte junctional proteins also relocalize. Before the initiation of cardiomyocyte delamination to form the trabecular layer, Crb2a is expressed in all ventricular cardiomyocytes colocalizing with the junctional protein ZO-1. Subsequently, Crb2a becomes localized all along the apical membrane of compact layer cardiomyocytes and is downregulated by those delaminating. We show that blood flow and Nrg/ErbB2 signaling regulate these Crb2a localization changes. crb2a mutants display a multilayered wall with polarized cardiomyocytes, a unique phenotype. Our data further indicate that Crb2a regulates cardiac trabeculation by controlling the localization of tight and adherens junctions in cardiomyocytes. Importantly, transplantation data show that Crb2a controls trabeculation in a CM-autonomous manner. Altogether, our study reveals a critical role for Crb2a during cardiac development.Summary statementInvestigation of the Crumbs polarity protein Crb2a in zebrafish reveals a novel role in cardiac development via regulation of cell-cell adhesion and apicobasal polarity.

How cells tell up from down and stick together to construct multicellular tissues – interplay between apicobasal polarity and cell–cell adhesion

2021 ◽  
Vol 134 (21) ◽  
Author(s):  
Claudia G. Vasquez ◽  
Eva L. de la Serna ◽  
Alexander R. Dunn
Keyword(s):  
Cell Adhesion ◽  
Protein Complexes ◽  
Basic Function ◽  
Cell Junction ◽  
Evolutionary Innovation ◽  
Apicobasal Polarity ◽  
Complex Architectures ◽  
Main Components ◽  
Definition Of ◽  
Cell Cell

ABSTRACT Polarized epithelia define a topological inside and outside, and hence constitute a key evolutionary innovation that enabled the construction of complex multicellular animal life. Over time, this basic function has been elaborated upon to yield the complex architectures of many of the organs that make up the human body. The two processes necessary to yield a polarized epithelium, namely regulated adhesion between cells and the definition of the apicobasal (top–bottom) axis, have likewise undergone extensive evolutionary elaboration, resulting in multiple sophisticated protein complexes that contribute to both functions. Understanding how these components function in combination to yield the basic architecture of a polarized cell–cell junction remains a major challenge. In this Review, we introduce the main components of apicobasal polarity and cell–cell adhesion complexes, and outline what is known about their regulation and assembly in epithelia. In addition, we highlight studies that investigate the interdependence between these two networks. We conclude with an overview of strategies to address the largest and arguably most fundamental unresolved question in the field, namely how a polarized junction arises as the sum of its molecular parts.

scholarly journals The Role of MicroRNAs in Epidermal Barrier

2020 ◽  
Vol 21 (16) ◽  
pp. 5781
Author(s):  
Ai-Young Lee
Keyword(s):  
Cell Adhesion ◽  
Critical Role ◽  
Keratinocyte Differentiation ◽  
Epidermal Barrier ◽  
Barrier Integrity ◽  
Skin Lipids ◽  
Differentiation And Proliferation ◽  
The Impact ◽  
Cell Cell

MicroRNAs (miRNAs), which mostly cause target gene silencing via transcriptional repression and degradation of target mRNAs, regulate a plethora of cellular activities, such as cell growth, differentiation, development, and apoptosis. In the case of skin keratinocytes, the role of miRNA in epidermal barrier integrity has been identified. Based on the impact of key genetic and environmental factors on the integrity and maintenance of skin barrier, the association of miRNAs within epidermal cell differentiation and proliferation, cell–cell adhesion, and skin lipids is reviewed. The critical role of miRNAs in the epidermal barrier extends the use of miRNAs for control of relevant skin diseases such as atopic dermatitis, ichthyoses, and psoriasis via miRNA-based technologies. Most of the relevant miRNAs have been associated with keratinocyte differentiation and proliferation. Few studies have investigated the association of miRNAs with structural proteins of corneocytes and cornified envelopes, cell–cell adhesion, and skin lipids. Further studies investigating the association between regulatory and structural components of epidermal barrier and miRNAs are needed to elucidate the role of miRNAs in epidermal barrier integrity and their clinical implications.

scholarly journals Integrin β1-Mediated Cell–Cell Adhesion Augments Metformin-Induced Anoikis

2019 ◽  
Vol 20 (5) ◽  
pp. 1161
Author(s):  
Tingting An ◽  
Zhiming Zhang ◽  
Yuhuang Li ◽  
Jianqiao Yi ◽  
Wenhua Zhang ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Critical Role ◽  
Cell Aggregation ◽  
Integrin Β1 ◽  
P53 Family ◽  
Anti Cancer ◽  
Glucose Restriction ◽  
Line Drug ◽  
Cell Cell

Cell–cell adhesion plays an important role in regulation of cell proliferation, migration, survival, and drug sensitivity. Metformin, a first line drug for type 2 diabetes, has been shown to possess anti-cancer activities. However, whether cell–cell adhesion affects metformin anti-cancer activity is unknown. In this study, Microscopic and FACS analyses showed that metformin induced cancer cell–cell adhesion exemplified by cell aggregation and anoikis under glucose restriction. Furthermore, western blot and QPCR analyses revealed that metformin dramatically upregulated integrin β1 expression. Silencing of integrin β1 significantly disrupted cell aggregation and reduced anoikis induced by metformin. Moreover, we showed that p53 family member ΔNp63α transcriptionally suppressed integrin β1 expression and is responsible for metformin-mediated upregulation of integrin β1. In summary, this study reveals a novel mechanism for metformin anticancer activity and demonstrates that cell–cell adhesion mediated by integrin β1 plays a critical role in metformin-induced anoikis.

scholarly journals Implications of Nectin-like Molecule-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 in Cell-Cell Adhesion and Transmembrane Protein Localization in Epithelial Cells

2003 ◽  
Vol 278 (37) ◽  
pp. 35421-35427 ◽  
Author(s):  
Tatsushi Shingai ◽  
Wataru Ikeda ◽  
Shigeki Kakunaga ◽  
Koji Morimoto ◽  
Kyoji Takekuni ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cells ◽  
Protein Localization ◽  
Transmembrane Protein ◽  
Cell Cell

scholarly journals RhoGEF17—An Essential Regulator of Endothelial Cell Death and Growth

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 741
Author(s):  
Pamina Weber ◽  
Doris Baltus ◽  
Aline Jatho ◽  
Oliver Drews ◽  
Laura C. Zelarayan ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Adhesion ◽  
Target Genes ◽  
Critical Role ◽  
Nucleotide Exchange ◽  
Akt Phosphorylation ◽  
Nucleotide Exchange Factor ◽  
Endothelial Cell Death ◽  
A Cell ◽  
Cell Cell

The Rho guanine nucleotide exchange factor RhoGEF17 was described to reside in adherens junctions (AJ) in endothelial cells (EC) and to play a critical role in the regulation of cell adhesion and barrier function. The purpose of this study was to analyze signal cascades and processes occurring subsequent to AJ disruption induced by RhoGEF17 knockdown. Primary human and immortalized rat EC were used to demonstrate that an adenoviral-mediated knockdown of RhoGEF17 resulted in cell rounding and an impairment in spheroid formation due to an enhanced proteasomal degradation of AJ components. In contrast, β-catenin degradation was impaired, which resulted in an induction of the β-catenin-target genes cyclin D1 and survivin. RhoGEF17 depletion additionally inhibited cell adhesion and sheet migration. The RhoGEF17 knockdown prevented the cells with impeded cell–cell and cell–matrix contacts from apoptosis, which was in line with a reduction in pro-caspase 3 expression and an increase in Akt phosphorylation. Nevertheless, the cells were not able to proliferate as a cell cycle block occurred. In summary, we demonstrate that a loss of RhoGEF17 disturbs cell–cell and cell–substrate interaction in EC. Moreover, it prevents the EC from cell death and blocks cell proliferation. Non-canonical β-catenin signaling and Akt activation could be identified as a potential mechanism.

Rescuing the N-cadherin knockout by cardiac-specific expression of N- or E-cadherin

Development ◽  
2001 ◽  
Vol 128 (4) ◽  
pp. 459-469
Author(s):  
Y. Luo ◽  
M. Ferreira-Cornwell ◽  
H. Baldwin ◽  
I. Kostetskii ◽  
J. Lenox ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Heart Development ◽  
Critical Role ◽  
Embryonic Cells ◽  
Wild Type ◽  
Specific Expression ◽  
Developmental Defects ◽  
E Cadherin ◽  
Cell Cell

Cell-cell adhesion mediated by some members of the cadherin family is essential for embryonic survival. The N-cadherin-null embryo dies during mid-gestation, with multiple developmental defects. We show that N-cadherin-null embryos expressing cadherins using muscle-specific promoters, alpha- or beta-myosin heavy chain, are partially rescued. Somewhat surprisingly, either N-cadherin or E-cadherin was effective in rescuing the embryos. The rescued embryos exhibited an increased number of somites, branchial arches and the presence of forelimb buds; however, in contrast, brain development was severely impaired. In rescued animals, the aberrant yolk sac morphology seen in N-cadherin-null embryos was corrected, demonstrating that this phenotype was secondary to the cardiac defect. Dye injection studies and analysis of chimeric animals that have both wild-type and N-cadherin-null cells support the conclusion that obstruction of the cardiac outflow tract represents a major defect that is likely to be the primary cause of pericardial swelling seen in null embryos. Although rescued embryos were more developed than null embryos, they were smaller than wild-type embryos, even though the integrity of the cardiovascular system appeared normal. The smaller size of rescued embryos may be due, at least in part, to increased apoptosis observed in tissues not rescued by transgene expression, indicating that N-cadherin-mediated cell adhesion provides an essential survival signal for embryonic cells. Our data provide in vivo evidence that cadherin adhesion is essential for cell survival and for normal heart development. Our data also show that E-cadherin can functionally substitute for N-cadherin during cardiogenesis, suggesting a critical role for cadherin-mediated cell-cell adhesion, but not cadherin family member-specific signaling, at the looping stage of heart development.

scholarly journals Transcriptional suppression of AMPKα1 promotes breast cancer metastasis upon oncogene activation

2020 ◽  
Vol 117 (14) ◽  
pp. 8013-8021 ◽  
Author(s):  
Yong Yi ◽  
Deshi Chen ◽  
Juan Ao ◽  
Wenhua Zhang ◽  
Jianqiao Yi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Cancer Metastasis ◽  
Kinase Activity ◽  
Critical Role ◽  
Breast Cancer Metastasis ◽  
Transcription Control ◽  
Cell Cell

AMP-activated protein kinase (AMPK) functions as an energy sensor and is pivotal in maintaining cellular metabolic homeostasis. Numerous studies have shown that down-regulation of AMPK kinase activity or protein stability not only lead to abnormality of metabolism but also contribute to tumor development. However, whether transcription regulation of AMPK plays a critical role in cancer metastasis remains unknown. In this study, we demonstrate that AMPKα1 expression is down-regulated in advanced human breast cancer and is associated with poor clinical outcomes. Transcription of AMPKα1 is inhibited on activation of PI3K and HER2 through ΔNp63α. Ablation of AMPKα1 expression or inhibition of AMPK kinase activity leads to disruption of E-cadherin-mediated cell–cell adhesion in vitro and increased tumor metastasis in vivo. Furthermore, restoration of AMPKα1 expression significantly rescues PI3K/HER2-induced disruption of cell–cell adhesion, cell invasion, and cancer metastasis. Together, these results demonstrate that the transcription control is another layer of AMPK regulation and suggest a critical role for AMPK in regulating cell–cell adhesion and cancer metastasis.

scholarly journals The Cadherin-Catenin Complex Is Expressed Alternately with the Adenomatous Polyposis Coli Protein During Rat Incisor Amelogenesis

2000 ◽  
Vol 48 (3) ◽  
pp. 397-406 ◽  
Author(s):  
Barbara C. Sorkin ◽  
Mark Y. Wang ◽  
Justine M. Dobeck ◽  
Karen L. Albergo ◽  
Ziedonis Skobe
Keyword(s):  
Cell Adhesion ◽  
Adenomatous Polyposis Coli ◽  
Critical Role ◽  
Maturation Stage ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Adenomatous Polyposis Coli Protein ◽  
Rat Incisor ◽  
E Cadherin ◽  
Cell Cell

E-cadherin, a calcium-dependent cell-cell adhesion molecule, is expressed in highly specific spatiotemporal patterns throughout metazoan development, notably at sites of embryonic induction. E-cadherin also plays a critical role in regulating cell motility/ adhesion, cell proliferation, and apoptosis. We have used the continuously erupting rat incisor as a system for examining the expression of E-cadherin and the associated catenins [α-, β-, γ-catenin (plakoglobin) and p120ctn] during amelogenesis. Using immunhistochemical techniques, we observed expression of α-catenin and γ-catenin in ameloblasts throughout amelogenesis. In contrast, expression of E-cadherin, β-catenin, and p120ctn was strong in presecretory, transitional, and reduced stage ameloblasts (Stages I, III, and V) but was dramatically lower in secretory and maturation stage ameloblasts (Stages II and IV). This expression alternates with the expression pattern we previously reported for the adenomatous polyposis coli protein (APC), a tumor suppressor that competes with E-cadherin for binding to β-catenin. We suggest that alternate expression of APC and the cadherin-catenin complex is critical for the alterations in cell-cell adhesion and other differentiated cellular characteristics, such as cytoskeletal alterations, that are required for the formation of enamel by ameloblasts.

scholarly journals A Microtiter Assay for Quantifying Protein-Protein Interactions Associated with Cell-Cell Adhesion

2007 ◽  
Vol 12 (5) ◽  
pp. 683-693 ◽  
Author(s):  
Nicholas A. Graham ◽  
Melissa D. Pope ◽  
Tharathorn Rimchala ◽  
Beijing K. Huang ◽  
Anand R. Asthagiri
Keyword(s):  
Protein Complex ◽  
Crucial Role ◽  
Cell Biology ◽  
Transmembrane Protein ◽  
Critical Role ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dramatic Improvement ◽  
E Cadherin ◽  
Cell Cell

Cell-cell adhesions are a hallmark of epithelial tissues, and the disruption of these contacts plays a critical role in both the early and late stages of oncogenesis. The interaction between the transmembrane protein E-cadherin and the intracellular protein β-catenin plays a crucial role in the formation and maintenance of epithelial cell-cell contacts and is known to be downregulated in many cancers. The authors have developed a protein complex enzyme-linked immunosorbent assay (ELISA) that can quantify the amount of β-catenin bound to E-cadherin in unpurified whole-cell lysates with a Z′ factor of 0.74. The quantitative nature of the E-cadherin:β-catenin ELISA represents a dramatic improvement over the low-throughput assays currently used to characterize endogenous E-cadherin:β-catenin complexes. In addition, the protein complex ELISA format is compatible with standard sandwich ELISAs for parallel measurements of total levels of endogenous E-cadherin and β-catenin. In 2 case studies closely related to cancer cell biology, the authors use the protein complex ELISA and traditional sandwich ELISAs to provide a detailed, quantitative picture of the molecular changes occurring within adherens junctions in vivo. Because the E-cadherin: β-catenin protein complex plays a crucial role in oncogenesis, this protein complex ELISA may prove to be a valuable quantitative prognostic marker of tumor progression. ( Journal of Biomolecular Screening 2007:683-693)

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