scholarly journals TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Amrutha Patkunarajah ◽  
Jeffrey H Stear ◽  
Mirko Moroni ◽  
Lioba Schroeter ◽  
Jedrzej Blaszkiewicz ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Melanoma Cells ◽  
Transduction Pathway ◽  
Adhesion Properties ◽  
Mechanoelectrical Transduction ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
And Migration ◽  
Cell Substrate Adhesion ◽  
Cell Cell

Mechanoelectrical transduction is a cellular signalling pathway where physical stimuli are converted into electro-chemical signals by mechanically activated ion channels. We describe here the presence of mechanically activated currents in melanoma cells that are dependent on TMEM87a, which we have renamed Elkin1. Heterologous expression of this protein in PIEZO1-deficient cells, that exhibit no baseline mechanosensitivity, is sufficient to reconstitute mechanically activated currents. Melanoma cells lacking functional Elkin1 exhibit defective mechanoelectrical transduction, decreased motility and increased dissociation from organotypic spheroids. By analysing cell adhesion properties, we demonstrate that Elkin1 deletion is associated with increased cell-substrate adhesion and decreased homotypic cell-cell adhesion strength. We therefore conclude that Elkin1 supports a PIEZO1-independent mechanoelectrical transduction pathway and modulates cellular adhesions and regulates melanoma cell migration and cell-cell interactions.

Modulation of epidermal differentiation by epiligrin and integrin alpha 3 beta 1

1995 ◽  
Vol 108 (2) ◽  
pp. 831-838 ◽  
Author(s):  
B.E. Symington ◽  
W.G. Carter
Keyword(s):  
Cell Adhesion ◽  
Close Contact ◽  
Intercellular Adhesion ◽  
Epidermal Differentiation ◽  
Basal Cells ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
High Calcium ◽  
Cell Substrate Adhesion ◽  
Cell Cell

We previously reported that integrin alpha 3 beta 1 mediates epidermal intercellular adhesion as well as cell-substrate adhesion. P1B5, an anti-alpha 3 beta 1 specific monoclonal antibody, is a potent in vitro trigger of epidermal cell-cell adhesion and an inhibitor of cell-substrate adhesion. We now show that P1B5 specifically induces the intercellular localization of integrins alpha 2 beta 1 and alpha 3 beta 1, consistent with its role in inducing intercellular adhesion via these two integrins. P1F2, another anti-alpha 3 beta 1 antibody, does not induce either intercellular adhesion or intercellular accumulation of alpha 3 beta 1 and alpha 2 beta 1. Growth of epidermal cells in high calcium, known to induce epidermal differentiation, also induces intercellular accumulation of alpha 3 beta 1 and alpha 2 beta 1 and increased cell-cell adhesion. We therefore asked whether P1B5 treatment induces epidermal differentiation. P1B5 treatment induces changes consistent with epidermal differentiation, including increased involucrin expression, stratification, and production of squames. P1F2 treatment has none of these effects. In vivo, epidermal basal cells are in close contact with the epithelial basement membrane component epiligrin. Growth of keratinocytes on purified epiligrin but not other matrix components specifically reduces involucrin expression by P1B5-treated keratinocytes. These results suggest that integrin alpha 3 beta 1 has a unique role in epidermal differentiation, that the epitope recognized by P1B5 is involved in triggering this differentiation, and that keratinocyte adhesion to epiligrin inhibits alpha 3 beta 1-mediated differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Perturbation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members.

1994 ◽  
Vol 125 (6) ◽  
pp. 1371-1384 ◽  
Author(s):  
K Takeuchi ◽  
N Sato ◽  
H Kasahara ◽  
N Funayama ◽  
A Nagafuchi ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Plasma Membranes ◽  
Family Members ◽  
Initial Step ◽  
Functional Interaction ◽  
Adhesion Sites ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Substrate Adhesion ◽  
Cell Cell

To examine the functions of ERM family members (ezrin, radixin, and moesin), mouse epithelial cells (MTD-1A cells) and thymoma cells (L5178Y), which coexpress all of them, were cultured in the presence of antisense phosphorothioate oligonucleotides (PONs) complementary to ERM sequences. Immunoblotting revealed that the antisense PONs selectively suppressed the expression of each member. Immunofluorescence microscopy of these ezrin, radixin, or moesin "single-suppressed" MTD-1A cells revealed that the ERM family members are colocalized at cell-cell adhesion sites, microvilli, and cleavage furrows, where actin filaments are densely associated with plasma membranes. The ezrin/radixin/moesin antisense PONs mixture induced the destruction of both cell-cell and cell-substrate adhesion, as well as the disappearance of microvilli. Ezrin or radixin antisense PONs individually affected the initial step of the formation of both cell-cell and cell-substrate adhesion, but did not affect the microvilli structures. In sharp contrast, moesin antisense PONs did not singly affect cell-cell and cell-substrate adhesion, whereas it partly affected the microvilli structures. These data indicate that ezrin and radixin can be functionally substituted, that moesin has some synergetic functional interaction with ezrin and radixin, and that these ERM family members are involved in cell-cell and cell-substrate adhesion, as well as microvilli formation.

Positive regulation of cell-cell and cell-substrate adhesion by protein kinase A

2001 ◽  
Vol 114 (18) ◽  
pp. 3265-3272
Author(s):  
John D. Whittard ◽  
Steven K. Akiyama
Keyword(s):  
Cell Adhesion ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Receptor Activation ◽  
Intracellular Camp ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Β1 Integrins ◽  
Cell Substrate Adhesion ◽  
Cell Cell

Integrin receptor activation is an important regulatory mechanism for cell-substrate and cell-cell adhesion. In this study, we explore a signaling pathway activated by mAb 12G10, an antibody that can activate β1 integrins and induce integrin-mediated cell-cell and cell-substrate adhesion. We have found that the cAMP-dependent protein kinase (PKA) is required for both mAb 12G10-induced cell-cell and cell-substrate adhesion of HT-1080 cells. Binding of mAb 12G10 to β1 integrins stimulates an increase in intracellular cAMP levels and PKA activity, and a concomitant shift in the localization of the PKA type II regulatory subunits from the cytoplasm to areas where integrins expressing the 12G10 epitope are located. MAb 12G10-induced cell-cell adhesion was mimicked by a combination of clustering β1 integrins and elevating PKA activity with Sp-adenosine-3′,5′-cyclic monophosphorothioate or forskolin. We also show that two processes required for HT-1080 cell-cell adhesion, integrin clustering and F-actin polymerization are both dependent on PKA. Taken together, our data suggest that PKA plays a key role in the signaling pathway, resulting from activation of β1 integrins, and that this enzyme may be required for upregulation of cell-substrate and cell-cell adhesion.

scholarly journals Novel function for beta 1 integrins in keratinocyte cell-cell interactions.

1990 ◽  
Vol 110 (3) ◽  
pp. 803-815 ◽  
Author(s):  
H Larjava ◽  
J Peltonen ◽  
S K Akiyama ◽  
S S Yamada ◽  
H R Gralnick ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cell Adhesion ◽  
Cell Interactions ◽  
Cell Contact ◽  
Cell Contacts ◽  
Cultured Keratinocytes ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Substrate Adhesion ◽  
Cell Cell

We have examined the expression, localization, and function of beta 1 integrins on cultured human epidermal keratinocytes using polyclonal and monoclonal antibodies against the beta 1, alpha 2, alpha 3, and alpha 5 integrin subunits. The beta 1 polypeptide, common to all class 1 integrins, was localized primarily in areas of cell-cell contacts of cultured keratinocytes, as were alpha 2 and alpha 3 polypeptides, suggesting a possible role in cell-cell adhesion for these integrin polypeptides. In contrast, the fibronectin receptor alpha 5 subunit showed no such accumulations in regions of cell-cell contact but was more diffusely distributed in the keratinocyte plasma membrane, consistent with the absence of fibronectin at cell-cell contact sites. Colonies of cultured keratinocytes could be dissociated by treatment with monoclonal antibody specific to the beta 1 polypeptide. Such dissociation of cell-cell contacts also occurred under conditions where the monoclonal antibody had no effect on cell-substrate adhesion. Therefore, beta 1 integrin-dependent cell-cell adhesion can be inhibited without affecting other cell-adhesive interactions. Antibody treatment of keratinocytes maintained in either low (0.15 mM) or high (1.2 mM) CaCl2 also resulted in the loss of organization of intracellular F-actin filaments and beta 1 integrins, even when the anti-beta 1 monoclonal antibody had no dissociating effect on keratinocyte colonies at the higher calcium concentration. Our results indicate that beta 1 integrins play roles in the maintenance of cell-cell contacts between keratinocytes and in the organization of intracellular microfilaments. They suggest that in epithelial cells integrins can function in cell-cell interactions as well as in cell-substrate adhesion.

scholarly journals Evidence of signaling and adhesion roles for β-catenin in the sponge Ephydatia muelleri

2017 ◽  
Author(s):  
Klaske J. Schippers ◽  
Scott A. Nichols
Keyword(s):  
Cell Adhesion ◽  
Wnt Pathway ◽  
Focal Adhesions ◽  
Fundamental Difference ◽  
Limited Data ◽  
Adhesion Properties ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Substrate Adhesion ◽  
Ephydatia Muelleri

ABSTRACTβ-catenin acts as a transcriptional co-activator in the Wnt/β-catenin signaling pathway and a cytoplasmic effector in cadherin-based cell adhesion. These functions are ancient within animals, but the earliest steps in β-catenin evolution remain unresolved due to limited data from key lineages – sponges, ctenophores and placozoans. Previous studies in sponges have characterized β-catenin expression dynamics and used GSK3B antagonists to ectopically activate the Wnt/β-catenin pathway; both approaches rely upon untested assumptions about the conservation of β-catenin function and regulation in sponges. Here, we test these assumptions using an antibody raised against β-catenin from the sponge Ephydatia muelleri. We find that cadherin-complex genes co-precipitate with endogenous Em β-catenin from cell lysates, but that Wnt pathway components do not. However, through immunostaining we detect both cell boundary and nuclear populations, and we find evidence that Em β-catenin is a conserved substrate of GSK3B. Collectively, these data support conserved roles for Em β-catenin in both cell adhesion and Wnt signaling. Additionally, we find evidence for an Em β-catenin population associated with the distal ends of F-actin stress fibers in apparent cell-substrate adhesion structures that resemble focal adhesions. This finding suggests a fundamental difference in the adhesion properties of sponge tissues relative to other animals, in which the adhesion functions of β-catenin are typically restricted to cell-cell adhesions.

Low Intensity Ultrasound Induces Epithelial Cell Adhesion Responses

2020 ◽  
Vol 142 (9) ◽  
Author(s):  
Jormay Lim ◽  
Yeh-Shiu Chu ◽  
Ya-Cherng Chu ◽  
Chun-Min Lo ◽  
Jaw-Lin Wang
Keyword(s):  
Cell Adhesion ◽  
Cellular Responses ◽  
Mouse Mammary Gland ◽  
Low Intensity ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Low Intensity Ultrasound ◽  
Cell Substrate Adhesion ◽  
Mammary Gland Epithelial Cells ◽  
Dose Dependent

Abstract In this study, we investigated the cellular mechanosensitive responses to a low intensity ultrasound (LIUS) stimulation (ISATA = 1 mW/cm2, pressure = 10 kPa). The dose and temporal effects at cell–substrate adhesion (CSA) at the basal level and cell–cell adhesion (CCA) at the apical level are reported in detail. A model of mouse mammary gland epithelial cells (EpH4) and the phosphorylation of mechanosensitive 130 kDa Crk-associated substrate (p130CAS) as an indicator for cellular responses were used. The intensity of phospho-p130CAS was found to be dependent on LIUS stress level, and the p130CAS was phosphorylated after 1 min stimulation at CSA. The phospho-p130CAS was also found to increase significantly at CCA upon LIUS stimulation. We confirmed that the cellular responses to ultrasound are immediate and dose dependent. Ultrasound affects not only CSA but also CCA. An E-cadherin knockout (EpH4ECad−/−) model also confirmed that phosphorylation of p130CAS at CCA is related to E-cadherins.

scholarly journals The interplay of cell–cell and cell–substrate adhesion in collective cell migration

2014 ◽  
Vol 11 (100) ◽  
pp. 20140684 ◽  
Author(s):  
Chenlu Wang ◽  
Sagar Chowdhury ◽  
Meghan Driscoll ◽  
Carole A. Parent ◽  
S. K. Gupta ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Actin Polymerization ◽  
Collective Cell Migration ◽  
Cell Contacts ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Shapes ◽  
Cell Substrate Adhesion ◽  
Cell Cell

Collective cell migration often involves notable cell–cell and cell–substrate adhesions and highly coordinated motion of touching cells. We focus on the interplay between cell–substrate adhesion and cell–cell adhesion. We show that the loss of cell-surface contact does not significantly alter the dynamic pattern of protrusions and retractions of fast migrating amoeboid cells ( Dictyostelium discoideum ), but significantly changes their ability to adhere to other cells. Analysis of the dynamics of cell shapes reveals that cells that are adherent to a surface may coordinate their motion with neighbouring cells through protrusion waves that travel across cell–cell contacts. However, while shape waves exist if cells are detached from surfaces, they do not couple cell to cell. In addition, our investigation of actin polymerization indicates that loss of cell-surface adhesion changes actin polymerization at cell–cell contacts. To further investigate cell–cell/cell–substrate interactions, we used optical micromanipulation to form cell–substrate contact at controlled locations. We find that both cell-shape dynamics and cytoskeletal activity respond rapidly to the formation of cell–substrate contact.

Cell-cell and cell-substrate adhesion molecules

Pathology ◽  
1992 ◽  
Vol 24 ◽  
pp. 26
Author(s):  
M.A. Vadas ◽  
J.R. Gamble ◽  
Y. Khew-Goodall ◽  
P. Kaur
Keyword(s):  
Adhesion Molecules ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Substrate Adhesion ◽  
Cell Cell
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