scholarly journals Bves: prototype of a new class of cell adhesion molecules expressed during coronary artery development

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 2085-2093 ◽  
Author(s):  
Aya M. Wada ◽  
David E. Reese ◽  
David M. Bader
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Vascular System ◽  
Single Cells ◽  
Cell Contact ◽  
Epithelial Migration ◽  
C Terminus ◽  
Membrane Compartment ◽  
Vessel Development

Bves is a protein expressed in cells of the developing coronary vascular system, specifically in the proepicardium, migrating epithelial epicardium, delaminated vasculogenic mesenchyme and vascular smooth muscle cells. Here, we show that Bves protein undergoes a dynamic subcellular redistribution during coronary vessel development. Bves is a membrane protein with three predicted transmembrane helices, an extracellular C terminus and an intracellular N terminus, and is confined to the lateral membrane compartment of epithelial cells. When epicardial cells are dissociated into single cells in vitro, Bves accumulates in a perinuclear region until cells make contact, at which time Bves is trafficked to the cell membrane. Bves accumulates at points of cell/cell contact, such as filopodia and cell borders, before the appearance of E-cadherin, suggesting an early role in cell adhesion. While Bves shares no homology with any known adhesion molecule, transfection of Bves into L-cells readily confers adhesive behavior to these cells. Finally, Bves antibodies inhibit epithelial migration of vasculogenic cells from the proepicardium. This study provides direct evidence that Bves is a novel cell adhesion molecule and suggests a role for Bves in coronary vasculogenesis.

scholarly journals NEDD4 regulates ubiquitination and stability of the cell adhesion molecule IGPR-1 via lysosomal pathway

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Linzi Sun ◽  
Razie Amraei ◽  
Nader Rahimi
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
E3 Ligase ◽  
Hek 293 ◽  
Ww Domains ◽  
Ubiquitin E3 Ligase ◽  
C Terminus

Abstract Background The cell adhesion molecule IGPR-1 regulates various critical cellular processes including, cell–cell adhesion, mechanosensing and autophagy and plays important roles in angiogenesis and tumor growth; however, the molecular mechanism governing the cell surface levels of IGPR-1 remains unknown. Results In the present study, we used an in vitro ubiquitination assay and identified ubiquitin E3 ligase NEDD4 and the ubiquitin conjugating enzyme UbcH6 involved in the ubiquitination of IGPR-1. In vitro GST-pulldown and in vivo co-immunoprecipitation assays demonstrated that NEDD4 binds to IGPR-1. Over-expression of wild-type NEDD4 downregulated IGPR-1 and deletion of WW domains (1–4) of NEDD4 revoked its effects on IGPR-1. Knockdown of NEDD4 increased IGPR-1 levels in A375 melanoma cells. Deletion of 57 amino acids encompassing the polyproline rich (PPR) motifs on the C-terminus of IGPR-1 nullified its binding with NEDD4. Furthermore, we demonstrate that NEDD4 promotes K48- and K63-dependent polyubiquitination of IGPR-1. The NEDD4-mediated polyubiquitination of IGPR-1 stimulates lysosomal-dependent degradation of IGPR-1 as the treatment of cells with the lysosomal inhibitors, bafilomycine or ammonium chloride increased IGPR-1 levels ectopically expressed in HEK-293 cells and in multiple endogenously IGPR-1 expressing human skin melanoma cell lines. Conclusions NEDD4 ubiquitin E3 ligase binds to and mediates polyubiquitination of IGPR-1 leading to its lysosomal-dependent degradation. NEDD4 is a key regulator of IGPR-1 expression with implication in the therapeutic targeting of IGPR-1 in human cancers.

Chrysin Suppresses Vascular Endothelial Inflammation via Inhibiting the NF-κB Signaling Pathway

2018 ◽  
Vol 24 (3) ◽  
pp. 278-287 ◽  
Author(s):  
Shengnan Zhao ◽  
Minglu Liang ◽  
Yilong Wang ◽  
Ji Hu ◽  
Yi Zhong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Signaling Pathway ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Flavonoid Compound ◽  
Endothelial Inflammation ◽  
Wide Range

The vascular endothelium is a continuous layer of flat polygonal cells that are in direct contact with the blood and participate in responses to inflammation. Chrysin is a flavonoid compound extracted from plants of the genus Asteraceae with a wide range of pharmacological activities and physiological activities. Here, we studied the effects of chrysin on the regulation of the proadhesion and pro-inflammatory phenotypes of the endothelium both in vitro and in vivo. Our results revealed that chrysin strongly inhibited Tohoku Hospital Pediatrics-1 (THP-1) cell adhesion to primary human umbilical vein endothelial cells and concentration-dependently attenuated interleukin 1β-induced increases in intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin messenger RNA levels and ICAM-1 and VCAM-1 protein levels. Previous studies reported that nuclear factor κB (NF-κB) is important in the inflammatory response in endothelial cells, particularly in regulating adhesion molecules, and our data shed light on the mechanisms whereby chrysin suppressed endothelial inflammation via the NF-κB signaling pathway. In addition, our in vivo findings demonstrated the effects of chrysin in the permeability and inflammatory responses of the endothelium to inflammatory injury. Taken together, we conclude that chrysin inhibits endothelial inflammation both in vitro and in vivo, which could be mainly due to its inhibition of NF-κB signaling activation. In conclusion, chrysin may serve as a promising therapeutic candidate for inflammatory vascular diseases.

scholarly journals Cell adhesion molecule IGPR-1 activates AMPK connecting cell adhesion to autophagy

2020 ◽  
Vol 295 (49) ◽  
pp. 16691-16699
Author(s):  
Razie Amraei ◽  
Tooba Alwani ◽  
Rachel Xi-Yeen Ho ◽  
Zahra Aryan ◽  
Shawn Wang ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Cellular Assays ◽  
Iκb Kinase ◽  
Promising Therapeutic Target ◽  
A Cell ◽  
Subsequent Activation

Autophagy plays critical roles in the maintenance of endothelial cells in response to cellular stress caused by blood flow. There is growing evidence that both cell adhesion and cell detachment can modulate autophagy, but the mechanisms responsible for this regulation remain unclear. Immunoglobulin and proline-rich receptor-1 (IGPR-1) is a cell adhesion molecule that regulates angiogenesis and endothelial barrier function. In this study, using various biochemical and cellular assays, we demonstrate that IGPR-1 is activated by autophagy-inducing stimuli, such as amino acid starvation, nutrient deprivation, rapamycin, and lipopolysaccharide. Manipulating the IκB kinase β activity coupled with in vivo and in vitro kinase assays demonstrated that IκB kinase β is a key serine/threonine kinase activated by autophagy stimuli and that it catalyzes phosphorylation of IGPR-1 at Ser220. The subsequent activation of IGPR-1, in turn, stimulates phosphorylation of AMP-activated protein kinase, which leads to phosphorylation of the major pro-autophagy proteins ULK1 and Beclin-1 (BECN1), increased LC3-II levels, and accumulation of LC3 punctum. Thus, our data demonstrate that IGPR-1 is activated by autophagy-inducing stimuli and in response regulates autophagy, connecting cell adhesion to autophagy. These findings may have important significance for autophagy-driven pathologies such cardiovascular diseases and cancer and suggest that IGPR-1 may serve as a promising therapeutic target.

scholarly journals ANGI-13. PLEXIN-B2 FACILITATES DIFFUSE GLIOMA INVASION BY REGULATING CELL ADHESION AND ACTO-MYOSIN DYNAMICS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi32-vi32
Author(s):  
Yong Huang ◽  
Rut Tejero ◽  
Vivian Lee ◽  
Chrystian Junqueira Alves ◽  
Ramsey Foty ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Single Cells ◽  
Biomechanical Properties ◽  
Diffuse Glioma ◽  
Compensatory Mechanisms ◽  
Glioma Invasion ◽  
Altered Expression ◽  
Mutant Cells ◽  
Cell Cell

Abstract Diffuse invasion of glioblastoma (GBM) cells into brain tissue is a key factor for its high lethality. GBM cell migration is affected by functions of plexins, which are transmembrane receptors of semaphorins that regulate cell adhesion and cytoskeletal dynamics. Expression of Plexin-B2 is upregulated in GBM and correlates with malignancy. We show here that Plexin-B2 activity regulates biomechanical properties of GBM cells, promoting invasive growth. Plexin-B2 activity increased the capacity of GBM to invade as dispersed single cells by reducing the cell-cell adhesiveness between GBM cells, indicating that a major function of Plexin-B2 activity is to downregulate cell-cell adhesion systems. RNA-Seq analyses also revealed that GBM stem cells (GSC) with deletion of Plexin-B2 altered expression of genes related to cell adhesion and the matrisome, indicating compensatory mechanisms in cellular dynamics. Interestingly, in vivo intracranial transplant studies demonstrated that growth and invasion of Plexin-B2 mutant GSC was impaired, with mutant cells invading shorter distances and migrating mainly as groups of cells forming chains. Plexin-B2 mutant cells also were more likely to adhere to the vasculature, rather than to fiber tracts, suggesting altered biomechanical properties. This shift may be related to high stiffness of basal lamina of the vasculature, as Plexin-B2 KO cells have a preference for migration on stiff substrate in vitro. Intriguingly, the loss in Plexin-B2 expression also changed the distribution of the mechanosensor transction factor YAP, with high expression of Plexin-B2 correlating with increased nuclear YAP. Structure-function analyses revealed that the Ras-GAP domain as main signaling output of Plexin-B2. The Rap proteins are pleiotropic regulators of cell adhesion and actomysosin contractility. Our data also showed that overexpression of Plexin-B2 can lead to decreased levels of Rap1/Rap2. Thus, Plexin-B2 acts as a key regulator of the adhesion and contractility of GBM cells, thereby facilitating their diffuse invasion.

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