scholarly journals MCAM contributes to the establishment of cell autonomous polarity in myogenic and chondrogenic differentiation

2017 ◽  
Author(s):  
Artal Moreno-Fortuny ◽  
Laricia Bragg ◽  
Giulio Cossu ◽  
Urmas Roostalu
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Adhesion Molecule ◽  
Chondrogenic Differentiation ◽  
Cell Adhesion Molecule ◽  
Kinase Activity ◽  
Myoblast Fusion ◽  
Extracellular Signals

ABSTRACTCell polarity has a fundamental role in shaping the morphology of cells and growing tissues. Polarity is commonly thought to be established in response to extracellular signals. Here we used a minimal in vitro assay that enabled us to monitor the determination of cell polarity in myogenic and chondrogenic differentiation in the absence of external signalling gradients. We demonstrate that the initiation of cell polarity is regulated by melanoma cell adhesion molecule (MCAM). We found highly polarized localization of MCAM, Moesin (MSN), Scribble (SCRIB) and Van-Gogh-like 2 (VANGL2) at the distal end of elongating myotubes. Knockout of MCAM or elimination of its endocytosis motif does not impair the initiation of myogenesis or myoblast fusion, but prevents myotube elongation. MSN, SCRIB and VANGL2 remain uniformly distributed in MCAM knockout cells. We show that MCAM is also required at early stages of chondrogenic differentiation. In both myogenic and chondrogenic differentiation MCAM knockout leads to transcriptional downregulation of Scrib and enhanced MAP kinase activity. Our data demonstrates the importance of cell autonomous polarity in differentiation.

N-cadherin and N-CAM in myoblast fusion: compared localisation and effect of blockade by peptides and antibodies

1992 ◽  
Vol 103 (4) ◽  
pp. 897-906 ◽  
Author(s):  
R.M. Mege ◽  
D. Goudou ◽  
C. Diaz ◽  
M. Nicolet ◽  
L. Garcia ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Synthetic Peptide ◽  
Cell Adhesion Molecule ◽  
Myoblast Fusion ◽  
Immunogold Electron Microscopy ◽  
Dependent Cell ◽  
Leg Muscle

The expression and distribution of two cell adhesion molecules, N-cadherin and N-CAM, at the surface of cultured leg muscle cells from 11-day-old chicken embryos were studied and compared. N-cadherin, which was expressed by fusing myoblasts, was down-regulated on old myotubes while N-CAM was still present. Both molecules, as viewed by confocal microscopy, appeared to have coaccumulated at the areas of contact between fusing myoblasts. However, immunogold electron microscopy did not reveal significant colocalization of N-cadherin and N-CAM, and their segregation after antibody-induced patching suggested the absence of direct interactions between N-cadherin and N-CAM. The role of the Ca2+ dependent cell adhesion molecule N-cadherin in myogenesis was investigated. Myoblast fusion was inhibited (1) with a synthetic peptide containing the H-A-V sequence and (2) with a monoclonal anti-N-cadherin antibody, demonstrating that N-cadherin-mediated cell adhesion is required for myoblast fusion. Under the same conditions no effect of anti-N-CAM antibodies was observed. Taken together these observations suggest that N-cadherin, acting independently from N-CAM, is a major cell adhesion molecule involved in embryonic myoblast fusion in vitro.

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 Involvement of Integrin αvβ3and Cell Adhesion Molecule L1 in Transendothelial Migration of Melanoma Cells

2001 ◽  
Vol 12 (9) ◽  
pp. 2699-2710 ◽  
Author(s):  
Evelyn B. Voura ◽  
Ravi A. Ramjeesingh ◽  
Anthony M.P. Montgomery ◽  
Chi-Hung Siu
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Polyclonal Antibodies ◽  
Transendothelial Migration ◽  
Melanoma Cells ◽  
Vitro Assay ◽  
Adhesive Interactions

Tumor metastasis involves many stage-specific adhesive interactions. The expression of several cell adhesion molecules, notably the integrin αvβ3, has been associated with the metastatic potential of tumor cells. In this study, we used a novel in vitro assay to examine the role of αvβ3 in the transmigration of melanoma cells through a monolayer of human lung microvascular endothelial cells. Confocal microscopy revealed the presence of the integrin αvβ3 on melanoma membrane protrusions and pseudopods penetrating the endothelial junction. αvβ3 was also enriched in heterotypic contacts between endothelial cells and melanoma cells. Transendothelial migration of melanoma cells was inhibited by either a cyclic Arg-Gly-Asp peptide or the anti-αvβ3monoclonal antibody LM609. Although both platelet endothelial cell adhesion molecule-1 and L1 are known to bind integrin αvβ3, only L1 serves as a potential ligand for αvβ3 during melanoma transendothelial migration. Also, polyclonal antibodies against L1 partially inhibited the transendothelial migration of melanoma cells. However, addition of both L1 and αvβ3 antibodies did not show additive effects, suggesting that they are components of the same adhesion system. Together, the data suggest that interactions between the integrin αvβ3 on melanoma cells and L1 on endothelial cells play an important role in the transendothelial migration of melanoma cells.

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