scholarly journals Talin-bound NPLY motif recruits integrin-signaling adapters to regulate cell spreading and mechanosensing

2014 ◽  
Vol 205 (2) ◽  
pp. 265-281 ◽  
Author(s):  
Perrine Pinon ◽  
Jenita Pärssinen ◽  
Patricia Vazquez ◽  
Michael Bachmann ◽  
Rolle Rahikainen ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Cell Spreading ◽  
Immune Defense ◽  
Adapter Protein ◽  
Sequence Motifs ◽  
Cell Matrix ◽  
Pathological Conditions ◽  
Dependent Cell ◽  
Cell Matrix Adhesion ◽  
Adjacent Sequence

Integrin-dependent cell adhesion and spreading are critical for morphogenesis, tissue regeneration, and immune defense but also tumor growth. However, the mechanisms that induce integrin-mediated cell spreading and provide mechanosensing on different extracellular matrix conditions are not fully understood. By expressing β3-GFP-integrins with enhanced talin-binding affinity, we experimentally uncoupled integrin activation, clustering, and substrate binding from its function in cell spreading. Mutational analysis revealed Tyr747, located in the first cytoplasmic NPLY747 motif, to induce spreading and paxillin adapter recruitment to substrate- and talin-bound integrins. In addition, integrin-mediated spreading, but not focal adhesion localization, was affected by mutating adjacent sequence motifs known to be involved in kindlin binding. On soft, spreading-repellent fibronectin substrates, high-affinity talin-binding integrins formed adhesions, but normal spreading was only possible with integrins competent to recruit the signaling adapter protein paxillin. This proposes that integrin-dependent cell–matrix adhesion and cell spreading are independently controlled, offering new therapeutic strategies to modify cell behavior in normal and pathological conditions.

scholarly journals Zasp is required for the assembly of functional integrin adhesion sites

2007 ◽  
Vol 179 (7) ◽  
pp. 1583-1597 ◽  
Author(s):  
Klodiana Jani ◽  
Frieder Schöck
Keyword(s):  
Focal Adhesions ◽  
Myotendinous Junction ◽  
Lim Domain ◽  
Transmembrane Receptors ◽  
Cell Matrix ◽  
Adhesion Sites ◽  
Alternatively Spliced ◽  
Dependent Cell ◽  
Cell Matrix Adhesion ◽  
Myotendinous Junctions

The integrin family of heterodimeric transmembrane receptors mediates cell–matrix adhesion. Integrins often localize in highly organized structures, such as focal adhesions in tissue culture and myotendinous junctions in muscles. Our RNA interference screen for genes that prevent integrin-dependent cell spreading identifies Z band alternatively spliced PDZ-motif protein (zasp), encoding the only known Drosophila melanogaster Alp/Enigma PDZ-LIM domain protein. Zasp localizes to integrin adhesion sites and its depletion disrupts integrin adhesion sites. In tissues, Zasp colocalizes with βPS integrin in myotendinous junctions and with α-actinin in muscle Z lines. Zasp also physically interacts with α-actinin. Fly larvae lacking Zasp do not form Z lines and fail to recruit α-actinin to the Z line. At the myotendinous junction, muscles detach in zasp mutants with the onset of contractility. Finally, Zasp interacts genetically with integrins, showing that it regulates integrin function. Our observations point to an important function for Zasp in the assembly of integrin adhesion sites both in cell culture and in tissues.

scholarly journals The integrin cytoplasmic domain-associated protein ICAP-1 binds and regulates Rho family GTPases during cell spreading

2002 ◽  
Vol 156 (2) ◽  
pp. 377-388 ◽  
Author(s):  
Simona Degani ◽  
Fiorella Balzac ◽  
Mara Brancaccio ◽  
Simona Guazzone ◽  
Saverio Francesco Retta ◽  
...  
Keyword(s):  
Cell Spreading ◽  
Cytoplasmic Domain ◽  
Nih3t3 Cells ◽  
Cell Matrix ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
First Time ◽  
Cell Matrix Adhesion

Using two-hybrid screening, we isolated the integrin cytoplasmic domain-associated protein (ICAP-1), an interactor for the COOH terminal region of the β1A integrin cytoplasmic domain. To investigate the role of ICAP-1 in integrin-mediated adhesive function, we expressed the full-length molecule in NIH3T3 cells. ICAP-1 expression strongly prevents NIH3T3 cell spreading on extracellular matrix. This inhibition is transient and can be counteracted by coexpression of a constitutively activated mutant of Cdc42, suggesting that ICAP-1 acts upstream of this GTPase. In addition, we found that ICAP-1 binds both to Cdc42 and Rac1 in vitro, and its expression markedly inhibits activation of these GTPases during integrin-mediated cell adhesion to fibronectin as detected by PAK binding assay. In the attempt to define the molecular mechanism of this inhibition, we show that ICAP-1 reduces both the intrinsic and the exchange factor–induced dissociation of GDP from Cdc42; moreover, purified ICAP-1 displaces this GTPase from cellular membranes. Together, these data show for the first time that ICAP-1 regulates Rho family GTPases during integrin-mediated cell matrix adhesion, acting as guanine dissociation inhibitor.

scholarly journals Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion

2009 ◽  
Vol 185 (3) ◽  
pp. 503-519 ◽  
Author(s):  
Stefanie Lapetina ◽  
Christopher C. Mader ◽  
Kazuya Machida ◽  
Bruce J. Mayer ◽  
Anthony J. Koleske
Keyword(s):  
Actin Polymerization ◽  
Molecular Mechanisms ◽  
Sh2 Domain ◽  
Cell Edge ◽  
Cell Matrix ◽  
C Terminus ◽  
Dependent Cell ◽  
Src Homology ◽  
Fibroblast Adhesion ◽  
Cell Matrix Adhesion

The molecular mechanisms by which the Abelson (Abl) or Abl-related gene (Arg) kinases interface with the actin polymerization machinery to promote cell edge protrusions during cell–matrix adhesion are unclear. In this study, we show that interactions between Arg and the Arp2/3 complex regulator cortactin are essential to mediate actin-based cell edge protrusion during fibroblast adhesion to fibronectin. Arg-deficient and cortactin knockdown fibroblasts exhibit similar defects in adhesion-dependent cell edge protrusion, which can be restored via reexpression of Arg and cortactin. Arg interacts with cortactin via both binding and catalytic events. The cortactin Src homology (SH) 3 domain binds to a Pro-rich motif in the Arg C terminus. Arg mediates adhesion-dependent phosphorylation of cortactin, creating an additional binding site for the Arg SH2 domain. Mutation of residues that mediate Arg–cortactin interactions abrogate the abilities of both proteins to support protrusions, and the Nck adapter, which binds phosphocortactin, is also required. These results demonstrate that interactions between Arg, cortactin, and Nck1 are critical to promote adhesion-dependent cell edge protrusions.

scholarly journals Vascular Endothelial-Cadherin Regulates Cytoskeletal Tension, Cell Spreading, and Focal Adhesions by Stimulating RhoA

2004 ◽  
Vol 15 (6) ◽  
pp. 2943-2953 ◽  
Author(s):  
Celeste M. Nelson ◽  
Dana M. Pirone ◽  
John L. Tan ◽  
Christopher S. Chen
Keyword(s):  
Adhesion Formation ◽  
Focal Adhesions ◽  
Cell Spreading ◽  
Cell Contact ◽  
Matrix Adhesion ◽  
Cell Matrix ◽  
Focal Adhesion Formation ◽  
Cytoskeletal Tension ◽  
Cell Matrix Adhesion ◽  
Cell Cell

Changes in vascular endothelial (VE)-cadherin–mediated cell-cell adhesion and integrin-mediated cell-matrix adhesion coordinate to affect the physical and mechanical rearrangements of the endothelium, although the mechanisms for such cross talk remain undefined. Herein, we describe the regulation of focal adhesion formation and cytoskeletal tension by intercellular VE-cadherin engagement, and the molecular mechanism by which this occurs. Increasing the density of endothelial cells to increase cell-cell contact decreased focal adhesions by decreasing cell spreading. This contact inhibition of cell spreading was blocked by disrupting VE-cadherin engagement with an adenovirus encoding dominant negative VE-cadherin. When changes in cell spreading were prevented by culturing cells on a micropatterned substrate, VE-cadherin–mediated cell-cell contact paradoxically increased focal adhesion formation. We show that VE-cadherin engagement mediates each of these effects by inducing both a transient and sustained activation of RhoA. Both the increase and decrease in cell-matrix adhesion were blocked by disrupting intracellular tension and signaling through the Rho-ROCK pathway. In all, these findings demonstrate that VE-cadherin signals through RhoA and the actin cytoskeleton to cross talk with cell-matrix adhesion and thereby define a novel pathway by which cell-cell contact alters the global mechanical and functional state of cells.

scholarly journals Arginylation-dependent regulation of a proteolytic product of talin is essential for cell–cell adhesion

2012 ◽  
Vol 197 (6) ◽  
pp. 819-836 ◽  
Author(s):  
Fangliang Zhang ◽  
Sougata Saha ◽  
Anna Kashina
Keyword(s):  
Cell Adhesion ◽  
Cell Attachment ◽  
Adhesion Formation ◽  
Cell Matrix ◽  
Intracellular Regulation ◽  
Dependent Cell ◽  
Cell Matrix Adhesion ◽  
Proteolytic Product ◽  
Cell Cell

Talin is a large scaffolding molecule that plays a major role in integrin-dependent cell–matrix adhesion. A role for talin in cell–cell attachment through cadherin has never been demonstrated, however. Here, we identify a novel calpain-dependent proteolytic cleavage of talin that results in the release of a 70-kD C-terminal fragment, which serves as a substrate of posttranslational arginylation. The intracellular levels of this fragment closely correlated with the formation of cell–cell adhesions, and this fragment localized to cadherin-containing cell–cell contacts. Moreover, reintroduction of this fragment rescued the cell–cell adhesion defects in arginyltransferase (Ate1) knockout cells, which normally have a very low level of this fragment. Arginylation of this fragment further enhanced its ability to rescue cell–cell adhesion formation. In addition, arginylation facilitated its turnover, suggesting a dual role of arginylation in its intracellular regulation. Thus, our work identifies a novel proteolytic product of talin that is regulated by arginylation and a new role of talin in cadherin-dependent cell–cell adhesion.

Anisotropic Strain Effects on Vascular Smooth Muscle Cell Physiology

2007 ◽  
Author(s):  
Vadim Tsvankin ◽  
Dmitry Belchenko ◽  
Devon Scott ◽  
Wei Tan
Keyword(s):  
Critical Role ◽  
Stem Cell Differentiation ◽  
Cell Physiology ◽  
Cell Matrix ◽  
Pathological Conditions ◽  
Wide Range ◽  
A Cell ◽  
Biological Development ◽  
Sense And Respond ◽  
Cell Matrix Adhesion

Biological development is a complex and highly-regulated process, a significant part of which is controlled by mechanostimulus, or the strain imparted on a cell by its environment. Mechanostimulus is important for stem cell differentiation, from cytoskeletal assembly to cell-cell and cell-matrix adhesion [1]. The mechanics of cells and tissues play a critical role in organisms, under both physiological and pathological conditions; abnormal mechanotransduction — the mechanism by which cells sense and respond to strain — has been implicated in a wide range of clinical pathologies [2,3].

Drosophila PS2 integrin mediates RGD-dependent cell-matrix interactions

Development ◽  
1992 ◽  
Vol 116 (1) ◽  
pp. 239-247 ◽  
Author(s):  
T.A. Bunch ◽  
D.L. Brower
Keyword(s):  
Divalent Cations ◽  
Calf Serum ◽  
Cell Spreading ◽  
Rgd Peptide ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Dependent Cell ◽  
Mediate Cell ◽  
Cell Matrix Interactions ◽  
Drosophila Cells

Integrins are a family of transmembrane glycoproteins that mediate cell-matrix and cell-cell interactions. We have transfected cultured Drosophila cells with genes that express the Drosophila PS2 integrin. We demonstrate that this integrin is expressed on the surface of the cells and can mediate cell spreading on an undefined component of fetal calf serum or on the purified vertebrate matrix molecules vitronectin and fibronectin. Additionally, PS2 integrin can cause cell spreading on RGD peptide. The spreading on matrix components or RGD peptide can be inhibited by soluble RGD peptide and is dependent on divalent cations.

scholarly journals Interaction between Galectin-3 and Integrins Mediates Cell-Matrix Adhesion in Endothelial Cells and Mesenchymal Stem Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5144
Author(s):  
Antonín Sedlář ◽  
Martina Trávníčková ◽  
Pavla Bojarová ◽  
Miluše Vlachová ◽  
Kristýna Slámová ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Vascular Tissue ◽  
Cell Functions ◽  
Matrix Adhesion ◽  
Cell Matrix ◽  
Selective Ligand ◽  
Galectin 3 ◽  
Cell Matrix Adhesion

Galectin-3 (Gal-3) is a β-galactoside-binding protein that influences various cell functions, including cell adhesion. We focused on the role of Gal-3 as an extracellular ligand mediating cell-matrix adhesion. We used human adipose tissue-derived stem cells and human umbilical vein endothelial cells that are promising for vascular tissue engineering. We found that these cells naturally contained Gal-3 on their surface and inside the cells. Moreover, they were able to associate with exogenous Gal-3 added to the culture medium. This association was reduced with a β-galactoside LacdiNAc (GalNAcβ1,4GlcNAc), a selective ligand of Gal-3, which binds to the carbohydrate recognition domain (CRD) in the Gal-3 molecule. This ligand was also able to detach Gal-3 newly associated with cells but not Gal-3 naturally present on cells. In addition, Gal-3 preadsorbed on plastic surfaces acted as an adhesion ligand for both cell types, and the cell adhesion was resistant to blocking with LacdiNAc. This result suggests that the adhesion was mediated by a binding site different from the CRD. The blocking of integrin adhesion receptors on cells with specific antibodies revealed that the cell adhesion to the preadsorbed Gal-3 was mediated, at least partially, by β1 and αV integrins—namely α5β1, αVβ3, and αVβ1 integrins.

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