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.

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.

scholarly journals A New Member of the Rho Family, Rnd1, Promotes Disassembly of Actin Filament Structures and Loss of Cell Adhesion

1998 ◽  
Vol 141 (1) ◽  
pp. 187-197 ◽  
Author(s):  
Catherine D. Nobes ◽  
Inger Lauritzen ◽  
Marie-Geneviève Mattei ◽  
Sonia Paris ◽  
Alan Hall ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Actin Cytoskeleton ◽  
Rho Gtpase ◽  
Focal Adhesions ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Rho Family ◽  
Cell Substrate Adhesion ◽  
Distinct Branch

Members of the Rho GTPase family regulate the organization of the actin cytoskeleton in response to extracellular growth factors. We have identified three proteins that form a distinct branch of the Rho family: Rnd1, expressed mostly in brain and liver; Rnd2, highly expressed in testis; and Rnd3/RhoE, showing a ubiquitous low expression. At the subcellular level, Rnd1 is concentrated at adherens junctions both in confluent fibroblasts and in epithelial cells. Rnd1 has a low affinity for GDP and spontaneously exchanges nucleotide rapidly in a physiological buffer. Furthermore, Rnd1 lacks intrinsic GTPase activity suggesting that in vivo, it might be constitutively in a GTP-bound form. Expression of Rnd1 or Rnd3/RhoE in fibroblasts inhibits the formation of actin stress fibers, membrane ruffles, and integrin-based focal adhesions and induces loss of cell–substrate adhesion leading to cell rounding (hence Rnd for “round”). We suggest that these proteins control rearrangements of the actin cytoskeleton and changes in cell adhesion.

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 Supervillin modulation of focal adhesions involving TRIP6/ZRP-1

2006 ◽  
Vol 174 (3) ◽  
pp. 447-458 ◽  
Author(s):  
Norio Takizawa ◽  
Tara C. Smith ◽  
Thomas Nebl ◽  
Jessica L. Crowley ◽  
Stephen J. Palmieri ◽  
...  
Keyword(s):  
Focal Adhesions ◽  
Stress Fibers ◽  
Regulatory Sequence ◽  
Interacting Protein ◽  
Substrate Adhesion ◽  
Lim Domains ◽  
Cell Substrate ◽  
Thyroid Receptor ◽  
And Function ◽  
Cell Substrate Adhesion

Cell–substrate contacts, called focal adhesions (FAs), are dynamic in rapidly moving cells. We show that supervillin (SV)—a peripheral membrane protein that binds myosin II and F-actin in such cells—negatively regulates stress fibers, FAs, and cell–substrate adhesion. The major FA regulatory sequence within SV (SV342-571) binds to the LIM domains of two proteins in the zyxin family, thyroid receptor–interacting protein 6 (TRIP6) and lipoma-preferred partner (LPP), but not to zyxin itself. SV and TRIP6 colocalize within large FAs, where TRIP6 may help recruit SV. RNAi-mediated decreases in either protein increase cell adhesion to fibronectin. TRIP6 partially rescues SV effects on stress fibers and FAs, apparently by mislocating SV away from FAs. Thus, SV interactions with TRIP6 at FAs promote loss of FA structure and function. SV and TRIP6 binding partners suggest several specific mechanisms through which the SV–TRIP6 interaction may regulate FA maturation and/or disassembly.

scholarly journals Stuck in the middle: Rac, adhesion, and cytokinesis

2012 ◽  
Vol 198 (5) ◽  
pp. 769-771 ◽  
Author(s):  
Tim Davies ◽  
Julie C. Canman
Keyword(s):  
Cell Adhesion ◽  
Small Gtpases ◽  
Gtpase Activating Protein ◽  
Contractile Ring ◽  
Division Plane ◽  
The Core ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Rho Family ◽  
Cell Substrate Adhesion

Rho family small GTPases (Rac, RhoA, and Cdc42) function at the core of cytokinesis, the physical division of one cell into two. In this issue, Bastos et al. (2012. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201204107) identify a new role for Rac inhibition: to release cell adhesion at the division plane and allow efficient constriction of the contractile ring. They show that the GTPase-activating protein, CYK4, suppresses equatorial cell substrate adhesion by inhibiting Rac and therefore its effectors ARFGEF7 and PAK1/2.

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 α-Tubulin K40 acetylation is required for contact inhibition of proliferation and cell–substrate adhesion

2014 ◽  
Vol 25 (12) ◽  
pp. 1854-1866 ◽  
Author(s):  
Andrea Aguilar ◽  
Lars Becker ◽  
Thomas Tedeschi ◽  
Stefan Heller ◽  
Carlo Iomini ◽  
...  
Keyword(s):  
Cell Density ◽  
Hippo Pathway ◽  
Focal Adhesions ◽  
Contact Inhibition ◽  
Inhibition Of Proliferation ◽  
Genetic Ablation ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
The Hippo Pathway ◽  
Cell Substrate Adhesion

Acetylation of α-tubulin on lysine 40 marks long-lived microtubules in structures such as axons and cilia, and yet the physiological role of α-tubulin K40 acetylation is elusive. Although genetic ablation of the α-tubulin K40 acetyltransferase αTat1 in mice did not lead to detectable phenotypes in the developing animals, contact inhibition of proliferation and cell–substrate adhesion were significantly compromised in cultured αTat1−/− fibroblasts. First, αTat1−/− fibroblasts kept proliferating beyond the confluent monolayer stage. Congruently, αTat1−/− cells failed to activate Hippo signaling in response to increased cell density, and the microtubule association of the Hippo regulator Merlin was disrupted. Second, αTat1−/− cells contained very few focal adhesions, and their ability to adhere to growth surfaces was greatly impaired. Whereas the catalytic activity of αTAT1 was dispensable for monolayer formation, it was necessary for cell adhesion and restrained cell proliferation and activation of the Hippo pathway at elevated cell density. Because α-tubulin K40 acetylation is largely eliminated by deletion of αTAT1, we propose that acetylated microtubules regulate contact inhibition of proliferation through the Hippo pathway.

Myoferlin depletion elevates focal adhesion kinase and paxillin phosphorylation and enhances cell-matrix adhesion in breast cancer cells

2015 ◽  
Vol 308 (8) ◽  
pp. C642-C649 ◽  
Author(s):  
B. N. Blackstone ◽  
R. Li ◽  
W. E. Ackerman ◽  
S. N. Ghadiali ◽  
H. M. Powell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Focal Adhesion Kinase ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Focal Adhesion ◽  
Breast Cancer Cells ◽  
Focal Adhesions ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Substrate Adhesion

Breast cancer is the second leading cause of malignant death among women. A crucial feature of metastatic cancers is their propensity to lose adhesion to the underlying basement membrane as they transition to a motile phenotype and invade surrounding tissue. Attachment to the extracellular matrix is mediated by a complex of adhesion proteins, including integrins, signaling molecules, actin and actin-binding proteins, and scaffolding proteins. Focal adhesion kinase (FAK) is pivotal for the organization of focal contacts and maturation into focal adhesions, and disruption of this process is a hallmark of early cancer invasive potential. Our recent work has revealed that myoferlin (MYOF) mediates breast tumor cell motility and invasive phenotype. In this study we demonstrate that noninvasive breast cancer cell lines exhibit increased cell-substrate adhesion and that silencing of MYOF using RNAi in the highly invasive human breast cancer cell line MDA-MB-231 also enhances cell-substrate adhesion. In addition, we detected elevated tyrosine phosphorylation of FAK (FAKY397) and paxillin (PAXY118), markers of focal adhesion protein activation. Morphometric analysis of PAX expression revealed that RNAi-mediated depletion of MYOF resulted in larger, more elongated focal adhesions, in contrast to cells transduced with a control virus (MDA-231LVC cells), which exhibited smaller focal contacts. Finally, MYOF silencing in MDA-MB-231 cells exhibited a more elaborate ventral cytoskeletal structure near focal adhesions, typified by pronounced actin stress fibers. These data support the hypothesis that MYOF regulates cell adhesions and cell-substrate adhesion strength and may account for the high degree of motility in invasive breast cancer cells.

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.

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