scholarly journals Zyxin-VASP interactions alter actin regulatory activity in zyxin-VASP complexes

2013 ◽  
Vol 18 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Jacob Grange ◽  
James Moody ◽  
Marc Ascione ◽  
Marc Hansen
Keyword(s):  
Actin Dynamics ◽  
Actin Assembly ◽  
Regulatory Activity ◽  
Substrate Adhesion ◽  
Lim Domains ◽  
Individual Interaction ◽  
Cell Substrate ◽  
And Function ◽  
Cell Substrate Adhesion ◽  
Cell Cell

AbstractCell-cell and cell-substrate adhesions are sites of dramatic actin rearrangements and where actin-membrane connections are tightly regulated. Zyxin-VASP complexes localize to sites of cell-cell and cell-substrate adhesion and function to regulate actin dynamics and actin-membrane connections at these sites. To accomplish these functions, zyxin recruits VASP to cellular sites via proline-rich binding sites near zyxin’s amino terminus. While the prevailing thought has been that zyxin simply acts as a scaffold protein for VASP binding, the identification of a LIM domain-VASP interaction could complicate this view. Here we assess how zyxin-VASP binding through both the proline rich motifs and the LIM domains alters specific VASP functions. We find that neither individual interaction alters VASP’s actin regulatory activities. In contrast, however, we find that full-length zyxin dramatically reduces VASPmediated actin bundling and actin assembly. Taken together, these results suggest a model where zyxin-VASP complexes occur in complex organizations with suppressed actin regulatory activity.

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 Common and Unique Transcription Signatures of YAP and TAZ in Gastric Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3667
Author(s):  
Yaelim Lee ◽  
Megan Finch-Edmondson ◽  
Hamizah Cognart ◽  
Bowen Zhu ◽  
Haiwei Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Dominant Role ◽  
Sequencing Analysis ◽  
Gastric Cancer Cells ◽  
Transcriptional Targets ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
And Function ◽  
Cell Substrate Adhesion

YAP and its paralog TAZ are the nuclear effectors of the Hippo tumour-suppressor pathway, and function as transcriptional co-activators to control gene expression in response to mechanical cues. To identify both common and unique transcriptional targets of YAP and TAZ in gastric cancer cells, we carried out RNA-sequencing analysis of overexpressed YAP or TAZ in the corresponding paralogous gene-knockouts (KOs), TAZ KO or YAP KO, respectively. Gene Ontology (GO) analysis of the YAP/TAZ-transcriptional targets revealed activation of genes involved in platelet biology and lipoprotein particle formation as targets that are common for both YAP and TAZ. However, the GO terms for cell-substrate junction were a unique function of YAP. Further, we found that YAP was indispensable for the gastric cancer cells to re-establish cell-substrate junctions on a rigid surface following prolonged culture on a soft substrate. Collectively, our study not only identifies common and unique transcriptional signatures of YAP and TAZ in gastric cancer cells but also reveals a dominant role for YAP over TAZ in the control of cell-substrate adhesion.

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

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 Contact inhibition of locomotion and mechanical cross-talk between cell–cell and cell–substrate adhesion determine the pattern of junctional tension in epithelial cell aggregates

2016 ◽  
Vol 27 (22) ◽  
pp. 3436-3448 ◽  
Author(s):  
Luke Coburn ◽  
Hender Lopez ◽  
Benjamin J. Caldwell ◽  
Elliott Moussa ◽  
Chloe Yap ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cross Talk ◽  
Contact Inhibition ◽  
Cell Junctions ◽  
Asymmetric Distribution ◽  
Cell Aggregates ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Substrate Adhesion ◽  
Cell Cell

We used a computational approach to analyze the biomechanics of epithelial cell aggregates—islands, stripes, or entire monolayers—that combines both vertex and contact-inhibition-of-locomotion models to include cell–cell and cell–substrate adhesion. Examination of the distribution of cell protrusions (adhesion to the substrate) in the model predicted high-order profiles of cell organization that agree with those previously seen experimentally. Cells acquired an asymmetric distribution of basal protrusions, traction forces, and apical aspect ratios that decreased when moving from the edge to the island center. Our in silico analysis also showed that tension on cell–cell junctions and apical stress is not homogeneous across the island. Instead, these parameters are higher at the island center and scale up with island size, which we confirmed experimentally using laser ablation assays and immunofluorescence. Without formally being a three-dimensional model, our approach has the minimal elements necessary to reproduce the distribution of cellular forces and mechanical cross-talk, as well as the distribution of principal stress in cells within epithelial cell aggregates. By making experimentally testable predictions, our approach can aid in mechanical analysis of epithelial tissues, especially when local changes in cell–cell and/or cell–substrate adhesion drive collective cell behavior.

Sign in / Sign up

Export Citation Format

Share Document