scholarly journals Multiple functions of the scaffold protein Discs large 5 in the control of growth, cell polarity and cell adhesion in Drosophila melanogaster

2020 ◽  
Author(s):  
Parvathy Venugopal ◽  
Hugo Veyssiere ◽  
Jean-Louis Couderc ◽  
Graziella Richard ◽  
Caroline Vachias ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Size ◽  
Cell Polarity ◽  
Hippo Pathway ◽  
Wing Disc ◽  
Animal Development ◽  
Discs Large ◽  
A Cell ◽  
The Impact ◽  
E Cadherin

Abstract Background : Scaffold proteins support a variety of key processes during animal development. Mutant mouse for the MAGUK protein Discs large 5 (Dlg5) presents a general growth impairment and moderate morphogenetic defects. Results: Here, we generated null mutants for Drosophila Dlg5 and show that it owns similar functions in growth and epithelial architecture. Dlg5 is required for growth at a cell autonomous level in several tissues and at the organism level, affecting cell size and proliferation. Our results are consistent with Dlg5 modulating hippo pathway in the wing disc, including the impact on cell size, a defect that is reproduced by the loss of yorkie. However, other observations indicate that Dlg5 regulates growth by at least another way that may involve Myc protein but nor PI3K neither TOR pathways. Moreover, epithelia cells mutant for Dlg5 also show a reduction of apical domain determinants, though not sufficient to induce a complete loss of cell polarity. Dlg5 is also essential, in the same cells, for the presence at Adherens junctions of N-Cadherin, but not E-Cadherin. Genetic analyses indicate that junction and polarity defects are independent. Conclusions : Together our data show that Dlg5 own several conserved functions that are independent of each other in regulating growth, cell polarity and cell adhesion. Moreover, they reveal a differential regulation of E-cadherin and N-cadherin apical localization.

scholarly journals Multiple functions of the scaffold protein Discs large 5 in the control of growth, cell polarity and cell adhesion in Drosophila melanogaster

2020 ◽  
Author(s):  
Parvathy Venugopal ◽  
Hugo Veyssiere ◽  
Jean-Louis Couderc ◽  
Graziella Richard ◽  
Caroline Vachias ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Size ◽  
Cell Polarity ◽  
Hippo Pathway ◽  
Wing Disc ◽  
Animal Development ◽  
Discs Large ◽  
A Cell ◽  
The Impact ◽  
E Cadherin

Abstract Background : Scaffold proteins support a variety of key processes during animal development. Mutant mouse for the MAGUK protein Discs large 5 (Dlg5) presents a general growth impairment and moderate morphogenetic defects. Results : Here, we generated null mutants for Drosophila Dlg5 and show that it owns similar functions in growth and epithelial architecture. Dlg5 is required for growth at a cell autonomous level in several tissues and at the organism level, affecting cell size and proliferation. Our results are consistent with Dlg5 modulating hippo pathway in the wing disc, including the impact on cell size, a defect that is reproduced by the loss of yorkie. However, other observations indicate that Dlg5 regulates growth by at least another way that may involve Myc protein but nor PI3K neither TOR pathways. Moreover, epithelia cells mutant for Dlg5 also show a reduction of apical domain determinants, though not sufficient to induce a complete loss of cell polarity. Dlg5 is also essential, in the same cells, for the presence at Adherens junctions of N-Cadherin, but not E-Cadherin. Genetic analyses indicate that junction and polarity defects are independent. Conclusions : Together our data show that Dlg5 own several conserved functions that are independent of each other in regulating growth, cell polarity and cell adhesion. Moreover, they reveal a differential regulation of E-cadherin and N-cadherin apical localization.

scholarly journals Multiple functions of the scaffold protein Discs large 5 in the control of growth, cell polarity and cell adhesion in Drosophila melanogaster

2020 ◽  
Author(s):  
Parvathy Venugopal ◽  
Hugo Veyssiere ◽  
Graziella Richard ◽  
Jean-Louis COUDERC ◽  
Caroline Vachias ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Hippo Pathway ◽  
Wing Disc ◽  
Small Cells ◽  
Animal Development ◽  
Discs Large ◽  
A Cell ◽  
Mutant Cells ◽  
E Cadherin

Abstract BackgroundScaffold proteins support a variety of key processes during animal development. Mutant mouse for the MAGUK protein Discs large 5 (Dlg5) presents a general growth impairment and moderate morphogenetic defects. ResultsHere, we generated null mutants for Drosophila Dlg5 and show that it owns similar functions. Dlg5 is required for growth at a cell autonomous level in several tissues and at the organism level, affecting cell size and proliferation. Our results are consistent with Dlg5 modulating hippo pathway in the wing disc, including the small cells, a defect that is reproduced by the loss of yorkie. However, other observations indicate that Dlg5 regulates growth by at least another way that may involve Myc protein but nor PI3K neither TOR pathways. Moreover, epithelial mutant cells for Dlg5 also show a reduction of apical domain determinants, though not sufficient to induce a complete loss of cell polarity. Dlg5 is also essential, in the same cells, for the presence at Adherens junctions of N-Cadherin, but not E-Cadherin. Genetic analyses indicate that junction and polarity defects are independent. Conclusions : Together our data show that Dlg5 own several conserved functions that are independent of each other in regulating growth, cell polarity and cell adhesion. Moreover, they reveal a differential regulation of E-cadherin and N-cadherin.

scholarly journals Multiple functions of the scaffold protein Discs large 5 in the control of growth, cell polarity and cell adhesion in Drosophila melanogaster

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Parvathy Venugopal ◽  
Hugo Veyssière ◽  
Jean-Louis Couderc ◽  
Graziella Richard ◽  
Caroline Vachias ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Adhesion ◽  
Cell Polarity ◽  
Scaffold Protein ◽  
Multiple Functions ◽  
Discs Large

scholarly journals Evidence for the Desmosomal Cadherin Desmoglein-3 in Regulating YAP and Phospho-YAP in Keratinocyte Responses to Mechanical Forces

2019 ◽  
Vol 20 (24) ◽  
pp. 6221 ◽  
Author(s):  
Jutamas Uttagomol ◽  
Usama Sharif Ahmad ◽  
Ambreen Rehman ◽  
Yunying Huang ◽  
Ana C. Laly ◽  
...  
Keyword(s):  
Target Genes ◽  
Hippo Pathway ◽  
Cyclic Strain ◽  
Cell Periphery ◽  
Mechanical Forces ◽  
Force Transmission ◽  
Direct Role ◽  
The Impact ◽  
Desmoglein 3 ◽  
E Cadherin

Desmoglein 3 (Dsg3) plays a crucial role in cell-cell adhesion and tissue integrity. Increasing evidence suggests that Dsg3 acts as a regulator of cellular mechanotransduction, but little is known about its direct role in mechanical force transmission. The present study investigated the impact of cyclic strain and substrate stiffness on Dsg3 expression and its role in mechanotransduction in keratinocytes. A direct comparison was made with E-cadherin, a well-characterized mechanosensor. Exposure of oral and skin keratinocytes to equiaxial cyclic strain promoted changes in the expression and localization of junction assembly proteins. The knockdown of Dsg3 by siRNA blocked strain-induced junctional remodeling of E-cadherin and Myosin IIa. Importantly, the study demonstrated that Dsg3 regulates the expression and localization of yes-associated protein (YAP), a mechanosensory, and an effector of the Hippo pathway. Furthermore, we showed that Dsg3 formed a complex with phospho-YAP and sequestered it to the plasma membrane, while Dsg3 depletion had an impact on both YAP and phospho-YAP in their response to mechanical forces, increasing the sensitivity of keratinocytes to the strain or substrate rigidity-induced nuclear relocation of YAP and phospho-YAP. Plakophilin 1 (PKP1) seemed to be crucial in recruiting the complex containing Dsg3/phospho-YAP to the cell surface since its silencing affected Dsg3 junctional assembly with concomitant loss of phospho-YAP at the cell periphery. Finally, we demonstrated that this Dsg3/YAP pathway has an influence on the expression of YAP1 target genes and cell proliferation. Together, these findings provide evidence of a novel role for Dsg3 in keratinocyte mechanotransduction.

scholarly journals Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254697
Author(s):  
Anne E. Roehrig ◽  
Kristina Klupsch ◽  
Juan A. Oses-Prieto ◽  
Selim Chaib ◽  
Stephen Henderson ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Molecular Mechanisms ◽  
Hippo Pathway ◽  
Contact Inhibition ◽  
Tumour Suppressor ◽  
Cell Cortex ◽  
Dependent Manner ◽  
A Cell ◽  
Cell Cell ◽  
Paf Complex

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition.

Synaptic development is controlled in the periactive zones of Drosophila synapses

Development ◽  
2000 ◽  
Vol 127 (19) ◽  
pp. 4157-4168 ◽  
Author(s):  
M. Sone ◽  
E. Suzuki ◽  
M. Hoshino ◽  
D. Hou ◽  
H. Kuromi ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Adhesion Molecule ◽  
Distinct Region ◽  
Still Life ◽  
Synaptic Development ◽  
Synaptic Growth ◽  
Neuromuscular Synapses ◽  
Discs Large ◽  
A Cell ◽  
Active Zones

A cell-adhesion molecule fasciclin 2 (FAS2), which is required for synaptic growth and still life (SIF), an activator of RAC, were found to localize in the surrounding region of the active zone, defining the periactive zone in Drosophila neuromuscular synapses. BetaPS integrin and discs large (DLG), both involved in synaptic development, also decorated the zone. However, shibire (SHI), the Drosophila dynamin that regulates endocytosis, was found in the distinct region. Mutant analyses showed that sif genetically interacted with Fas2 in synaptic growth and that the proper localization of SIF required FAS2, suggesting that they are components in related signaling pathways that locally function in the periactive zones. We propose that neurotransmission and synaptic growth are primarily regulated in segregated subcellular spaces, active zones and periactive zones, respectively.

scholarly journals A cell-size threshold limits cell polarity and asymmetric division potential

2019 ◽  
Vol 15 (10) ◽  
pp. 1078-1085 ◽  
Author(s):  
Lars Hubatsch ◽  
Florent Peglion ◽  
Jacob D. Reich ◽  
Nelio T. L. Rodrigues ◽  
Nisha Hirani ◽  
...  
Keyword(s):  
Cell Size ◽  
Cell Polarity ◽  
Asymmetric Division ◽  
A Cell ◽  
Size Threshold

scholarly journals Quantitative Differences in Levels of Immunohistochemical Biomarkers between Squamous Cell Carcinoma and Adenocarcinoma of the Uterine Cervix: Implications for Treatment Outcomes after Chemoradiotherapy

2020 ◽  
Author(s):  
RUI-YUN CHEN Chen ◽  
YING-CHUN LIN ◽  
JI-AN LIANG ◽  
Yao-Chin Hung ◽  
LIAN-SHUNG YEH ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Adhesion ◽  
Cell Carcinoma ◽  
Treatment Outcomes ◽  
Squamous Cell ◽  
Cox Regression ◽  
High Rate ◽  
Gynecology And Obstetrics ◽  
The Impact ◽  
E Cadherin

Abstract Introduction: This study compared the quantitative differences in immunohistochemical markers between uterine cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) and assessed the impact of these biomarkers on outcomes in patients treated with chemoradiotherapy (CRT).Method: This retrospective study included 118 patients (SCC in 76, AC in 42) who received definitive CRT. According to the International Federation of Gynecology and Obstetrics staging system, 14, 34, and 70 patients were classified as having stage IB3, II, and III disease, respectively. Baseline immunohistochemical biomarkers, including hypoxia, cell proliferation, cell adhesion, immunogenicity, inflammatory, and evasion of apoptosis biomarkers, were analyzed using tissue microarrays from biopsy specimens. The Mann-Whitney U test was carried out for quantitative analysis between SCC and AC. Cox regression analysis was used to examine the effects of the biomarkers and clinical parameters on treatment outcomes.Results: Using the H-scores of the biomarkers for SCC as a reference, increased expression of E-cadherin, calretinin, CAIX, and c-Myc and decreased levels of HIF-1α, VEGF, tumor necrosis factor-α, galectin-9, chemokine ligand 5, Bax, EGFR, and insulin-like growth factor 1 receptor were found in the patients with AC. A high E-cadherin (P = 0.002) and low Bax (P = 0.001) H-score were associated with inferior pelvic relapse-free survival. Conclusion: Cervical SCC exhibited strong expression of baseline immunohistochemical inflammatory, hypoxic, and angiogenesis biomarkers whereas the intensity of cell adhesion markers was more distinct in cervical AC. A high E-cadherin and a low Bax H-score were associated with a high rate of local relapse.

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