Ligand Diffusion Enables Force‐Independent Cell Adhesion via Activating α5β1 Integrin and Initiating Rac and RhoA Signaling

2020 ◽  
Vol 32 (29) ◽  
pp. 2002566 ◽  
Author(s):  
Leixiao Yu ◽  
Yong Hou ◽  
Wenyan Xie ◽  
Jose Luis Cuellar Camacho ◽  
Chong Cheng ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Rhoa Signaling ◽  
Ligand Diffusion ◽  
Α5β1 Integrin

scholarly journals Mena binds α5 integrin directly and modulates α5β1 function

2012 ◽  
Vol 198 (4) ◽  
pp. 657-676 ◽  
Author(s):  
Stephanie L. Gupton ◽  
Daisy Riquelme ◽  
Shannon K. Hughes-Alford ◽  
Jenny Tadros ◽  
Shireen S. Rudina ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Growth Factor Receptor ◽  
Focal Adhesions ◽  
Fibronectin Receptor ◽  
Focal Adhesion Proteins ◽  
Carboxy Terminal ◽  
Bidirectional Interactions ◽  
Dependent Processes ◽  
Α5β1 Integrin

Mena is an Ena/VASP family actin regulator with roles in cell migration, chemotaxis, cell–cell adhesion, tumor cell invasion, and metastasis. Although enriched in focal adhesions, Mena has no established function within these structures. We find that Mena forms an adhesion-regulated complex with α5β1 integrin, a fibronectin receptor involved in cell adhesion, motility, fibronectin fibrillogenesis, signaling, and growth factor receptor trafficking. Mena bound directly to the carboxy-terminal portion of the α5 cytoplasmic tail via a 91-residue region containing 13 five-residue “LERER” repeats. In fibroblasts, the Mena–α5 complex was required for “outside-in” α5β1 functions, including normal phosphorylation of FAK and paxillin and formation of fibrillar adhesions. It also supported fibrillogenesis and cell spreading and controlled cell migration speed. Thus, fibroblasts require Mena for multiple α5β1-dependent processes involving bidirectional interactions between the extracellular matrix and cytoplasmic focal adhesion proteins.

Fibronectin Distribution in Human Bone Marrow Stroma: Matrix Assembly and Tumor Cell Adhesion via α5β1 Integrin

1997 ◽  
Vol 230 (1) ◽  
pp. 111-120 ◽  
Author(s):  
D. Van der Velde-Zimmermann ◽  
M.A.M. Verdaasdonk ◽  
L.H.P.M. Rademakers ◽  
R.A. De Weger ◽  
J.G. Van den Tweel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Adhesion ◽  
Tumor Cell ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Bone Marrow Stroma ◽  
Matrix Assembly ◽  
Tumor Cell Adhesion ◽  
Marrow Stroma ◽  
Α5β1 Integrin

scholarly journals Fibronectin-mediated upregulation of α5β1 integrin and cell adhesion during differentiation of mouse embryonic stem cells

2011 ◽  
Vol 5 (1) ◽  
pp. 73-82 ◽  
Author(s):  
Pimchanok Pimton ◽  
Saheli Sarkar ◽  
Nidhi Sheth ◽  
Anat Perets ◽  
Cezary Marcinkiewicz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Α5β1 Integrin

Localization of BCR-ABL to F-actin regulates cell adhesion but does not attenuate CML development

Blood ◽  
2003 ◽  
Vol 102 (6) ◽  
pp. 2220-2228 ◽  
Author(s):  
Jason A. Wertheim ◽  
Samanthi A. Perera ◽  
Daniel A. Hammer ◽  
Ruibao Ren ◽  
David Boettiger ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Function Analysis ◽  
Coiled Coil ◽  
Myelogenous Leukemia ◽  
Actin Binding ◽  
Murine Bone Marrow ◽  
Actin Binding Domain ◽  
Transplantation Assay ◽  
Α5β1 Integrin ◽  
Actin Localization

Abstract We have previously found that P210BCR-ABL increases the adhesion of hematopoietic cell lines to fibronectin by a mechanism that is independent of tyrosine kinase activity. To investigate the pathway(s) by which P210BCR-ABL influences cell adhesion, we used a quantitative cell adhesion device that can discern small changes in cell adhesion to assay P210BCR-ABL with mutations in several critical domains. We expressed P210BCR-ABL mutants in 32D myeloblast cells and found that binding to fibronectin is mediated primarily by the α5β1 integrin. We performed a structure/function analysis to map domains important for cell adhesion. Increased adhesion was mediated by 3 domains: (1) the N-terminal coiled-coil domain that facilitates oligomerization and F-actin localization; (2) bcr sequences between aa 163 to 210; and (3) F-actin localization through the C-terminal actin-binding domain of c-abl. We compared our adhesion results with the ability of these mutants to cause a chronic myelogenous leukemia (CML)–like disease in a murine bone marrow transplantation assay and found that adhesion to fibronectin did not correlate with the ability of these mutants to cause CML. Together, our results suggest that F-actin localization may play a pivotal role in modulating adhesion but that it is dispensable for the development of CML.

scholarly journals RGD-independent Cell Adhesion via a Tissue Transglutaminase-Fibronectin Matrix Promotes Fibronectin Fibril Deposition and Requires Syndecan-4/2 and α5β1 Integrin Co-signaling

2010 ◽  
Vol 285 (51) ◽  
pp. 40212-40229 ◽  
Author(s):  
Zhuo Wang ◽  
Russell J. Collighan ◽  
Stephane R. Gross ◽  
Erik H. J. Danen ◽  
Gertraud Orend ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Tissue Transglutaminase ◽  
Fibronectin Matrix ◽  
Α5β1 Integrin

Characterization of plasminogen as an adhesive ligand for integrins αMβ2 (Mac-1) and α5β1 (VLA-5)

Blood ◽  
2004 ◽  
Vol 104 (3) ◽  
pp. 719-726 ◽  
Author(s):  
Valeryi K. Lishko ◽  
Valery V. Novokhatny ◽  
Valentin P. Yakubenko ◽  
Helen V. Skomorovska-Prokvolit ◽  
Tatiana P. Ugarova
Keyword(s):  
Cell Adhesion ◽  
Aminocaproic Acid ◽  
Genetically Engineered ◽  
Plasmin Activity ◽  
Hek 293 ◽  
293 Cells ◽  
Blood Neutrophils ◽  
Α5β1 Integrin ◽  
Extracellular Proteolysis

AbstractPlasminogen (Pg) has been implicated in many biologic processes involving extracellular proteolysis. We investigated whether Pg, by virtue of its capacity to be deposited within the extracellular matrix, can serve as a ligand for cell surface integrins. We report here that Pg supports cell adhesion by engaging integrins αMβ2 and α5β1. The immobilized Glu-Pg, but not its derivatives with the N-terminal peptide lacking, plasmin and Lys-Pg, supported efficient adhesion that was abolished by anti-αMβ2 and anti-α5β1 integrin-specific monoclonal antibodies (mAbs). In addition, lysine binding sites of Glu-Pg contributed to cell adhesion inasmuch as tranexamic acid and ϵ-aminocaproic acid inhibited cell adhesion. The involvement of αMβ2 and α5β1 in adhesion to Glu-Pg was demonstrable with blood neutrophils, U937 monocytoid cells, and genetically engineered αMβ2-transfected human embryonic kidney (HEK) 293 cells. In αMβ2, the αMI-domain is the binding site for Glu-Pg because the “I-less” form of αMβ2 did not support cell adhesion and the recombinant αMI-domain bound Glu-Pg directly. In comparison with cell adhesion, the binding of soluble Glu-Pg to cells and the concomitant generation of plasmin activity was inhibited by anti-α5β1 but not by anti-αMβ2. These findings identify Glu-Pg as an adhesive ligand for integrins αMβ2 and α5β1 and suggest that α5β1 may participate in the binding of soluble Glu-Pg and assist in its activation.

A proangiogenic peptide derived from vascular endothelial growth factor receptor-1 acts through α5β1 integrin

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3479-3488 ◽  
Author(s):  
Simonetta Soro ◽  
Angela Orecchia ◽  
Lucia Morbidelli ◽  
Pedro Miguel Lacal ◽  
Veronica Morea ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Growth Factors ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Α5β1 Integrin

Abstract Vascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase receptor for growth factors of the VEGF family. Endothelial cells express a membrane-bound and a soluble variant of this protein, the latter being mainly considered as a negative regulator of VEGF-A signaling. We previously reported that the soluble form is deposited in the extracellular matrix produced by endothelial cells in culture and is able to promote cell adhesion and migration through binding to α5β1 integrin. In this study, we demonstrate that the Ig-like domain II of VEGFR-1, which contains the binding determinants for the growth factors, is involved in the interaction with α5β1 integrin. To identify domain regions involved in integrin binding, we designed 12 peptides putatively mimicking the domain II surface and tested their ability to inhibit α5β1-mediated endothelial cell adhesion to soluble VEGFR-1 and directly support cell adhesion. One peptide endowed with both these properties was identified and shown to inhibit endothelial cell migration toward soluble VEGFR-1 as well. This peptide directly binds α5β1 integrin, but not VEGF-A, inducing endothelial cell tubule formation in vitro and neoangiogenesis in vivo. Alanine scanning mutagenesis of the peptide defined which residues were responsible for its biologic activity and integrin binding.

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