Regulation of β1 Integrin-Mediated Adhesive Functions

1993 ◽  
pp. 45-61
Author(s):  
Francisco Sánchez-Madrid ◽  
Alicia G. Arroyo ◽  
Miguel R. Campanero ◽  
Paloma Sánchez-Mateos
Keyword(s):  
Β1 Integrin

Cell-matrix interactions in the early mouse embryo

1992 ◽  
Vol 50 (1) ◽  
pp. 600-601
Author(s):  
A.E. Sutherland ◽  
P.G. Calarco ◽  
C.H. Damsky
Keyword(s):  
Mouse Embryo ◽  
Giant Cells ◽  
Blastocyst Stage ◽  
Integrin Subunit ◽  
Β1 Integrin ◽  
Cell Stage ◽  
Early Mouse Embryo ◽  
Migratory Activity ◽  
Early Mouse ◽  
Cell Matrix Interactions

Cell-extracellular matrix (ECM) interactions mediated by the integrin family of receptors are critical for morphogenesis and may also play a regulatory role in differentiation during early development. We have examined the onset of expression of individual integrin subunit proteins in the early mouse embryo, and their roles in early morphogenetic events. As detected by immunoprecipitation, the α6, αV, β1, and β3 subunits are detected as early as the 4-cell stage, α5 at the hatched blastocyst stage and αl and α3 following blastocyst attachment. We tested the role of these integrins in the attachment and migratory activity of two cell populations of the early mouse embryo: the trophoblast giant cells, which invade the uterine stroma and ultimately contribute to the chorio-allantoic placenta, and the parietal endoderm, which migrates over the inner surface of the trophoblast and ultimately forms Reichert's membrane and the parietal yolk sac. Experiments were done in serum-free medium on substrates coated with laminin (Ln) and fibronectin (Fn). Trophoblast outgrowth occurs on Ln and its E8 fragment (long arm), but not on the E1’ fragment (cross region) (Figs. 1, 2 ). This outgrowth is inhibited by anti-E8, anti-Ln, and by the anti-β1 family antiserum anti-ECMR, but not by anti-αV or the function-perturbing GoH3 antibody that recognizes the α6/β1 integrin, a major Ln (E8) receptor. This suggests that trophoblast outgrowth on Ln or E8 is mediated by a different β1 integrin such as α3/β1. Early stages of trophoblast outgrowth (up to 48 hours) on Fn are inhibited by anti-Fn and by function-perturbing anti-αV antibodies, whereas at later times outgrowth becomes insensitive to anti-αV but remains sensitive to the anti-β1 family antiserum anti-ECMr, indicating that trophoblast cells modulate their interaction with Fn during outgrowth. Trophoblast outgrowth on vitronectin (Vn) is sensitive to anti-αV antibodies throughout the 5-day period examined.

Laminin 521 Modulates the Сytotoxic Effect of 5-Fluorouracil on Colorectal Cancer HT29 Cells

2019 ◽  
Vol 35 (6) ◽  
pp. 73-79
Author(s):  
A. Turchinovich ◽  
I.M. Tsypina ◽  
V.G. Zgoda ◽  
S.V. Nikulin ◽  
D.V. Maltseva
Keyword(s):  
Colorectal Cancer ◽  
Cytotoxic Effect ◽  
Mechanisms Of Action ◽  
Ht29 Cell ◽  
Β1 Integrin ◽  
Russian Science ◽  
Apoptotic Gene ◽  
Ht29 Cells ◽  
First Time ◽  
Ht29 Cell Line

The cytotoxic effect of 5-fluorouracil (5FU) and regorafenib (RF)-drugs with different mechanisms of action used to treat colorectal cancer-on the HT29 cell line when cultured on plastic and laminin 521 (LM-521) has been studied. It was shown for the first time that LM-521 can increase the sensitivity of tumor cells to 5FU. Based on the analysis of the transcriptome and proteome, a possible mechanism of the observed effect of LM-521 on HT29 cell viability was proposed. The interaction of β1-containing integrins on the cell surface with LM-521 can activate the FAK/PI3K/Akt signaling pathways, promote phosphorylation of the YAP transcription coactivator and its binding to a complex with the 14-3-3σ protein. The formation of such complex leads to the YAP retention in the cytoplasm, prevents its transport to the nucleus and the activation of anti-apoptotic gene transcription. apoptosis, β1 integrin, colorectal cancer, laminin 521 (laminin-11), regorafenib, 5-fluorouracil, HT29, ITGB1, LAMA5, YAP, SFN, 14-3-3σ The study was funded by the Russian Science Foundation (Project 17-14-01338).

scholarly journals SPEG binds with desmin and its deficiency causes defects in triad and focal adhesion proteins

2020 ◽  
Author(s):  
Shiyu Luo ◽  
Qifei Li ◽  
Jasmine Lin ◽  
Quinn Murphy ◽  
Isabelle Marty ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Skeletal Muscles ◽  
Striated Muscle ◽  
Calcium Handling ◽  
Intermediate Filament Protein ◽  
Β1 Integrin ◽  
Adhesion Proteins ◽  
Focal Adhesion Proteins ◽  
Early Endosomes

Abstract SPEG, a member of the myosin light chain kinase family, is localized at the level of triad surrounding myofibrils in skeletal muscles. In humans, SPEG mutations are associated with centronuclear myopathy and cardiomyopathy. Using a striated muscle specific Speg-knockout (KO) mouse model, we have previously shown that SPEG is critical for triad maintenance and calcium handling. Here we further examined the molecular function of SPEG and characterized the effects of SPEG deficiency on triad and focal adhesion proteins. We used yeast two-hybrid assay, and identified desmin, an intermediate filament protein, to interact with SPEG and confirmed this interaction by co-immunoprecipitation. Using domain-mapping assay, we defined that Ig-like and fibronectin III domains of SPEG interact with rod domain of desmin. In skeletal muscles, SPEG depletion leads to desmin aggregates in vivo and a shift in desmin equilibrium from soluble to insoluble fraction. We also profiled the expression and localization of triadic proteins in Speg-KO mice using western blot and immunofluorescence. The amounts of RyR1 and triadin were markedly reduced, whereas DHPRα1, SERCA1, and triadin were abnormally accumulated in discrete areas of Speg-KO myofibers. In addition, Speg-KO muscles exhibited internalized vinculin and β1 integrin, both of which are critical components of the focal adhesion complex. Further, β1 integrin was abnormally accumulated in early endosomes of Speg-KO myofibers. These results demonstrate that SPEG-deficient skeletal muscles exhibit several pathological features similar to those seen in MTM1 deficiency. Defects of shared cellular pathways may underlie these structural and functional abnormalities in both types of diseases.

scholarly journals Endothelial β1 Integrin-Mediated Adaptation to Myocardial Ischemia

2021 ◽  
Author(s):  
Carina Henning ◽  
Anna Branopolski ◽  
Paula Follert ◽  
Oksana Lewandowska ◽  
Aysel Ayhan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Integrin Subunit ◽  
Β1 Integrin ◽  
Human Coronary Artery ◽  
Tetrazolium Chloride ◽  
Magnetic Resonance Imaging Mri ◽  
Interfering Rna

Abstract Background Short episodes of myocardial ischemia can protect from myocardial infarction. However, the role of endothelial β1 integrin in these cardioprotective ischemic events is largely unknown. Objective In this study we investigated whether endothelial β1 integrin is required for cardiac adaptation to ischemia and protection from myocardial infarction. Methods Here we introduced transient and permanent left anterior descending artery (LAD) occlusions in mice. We inhibited β1 integrin by intravenous injection of function-blocking antibodies and tamoxifen-induced endothelial cell (EC)-specific deletion of Itgb1. Furthermore, human ITGB1 was silenced in primary human coronary artery ECs using small interfering RNA. We analyzed the numbers of proliferating ECs and arterioles by immunohistochemistry, determined infarct size by magnetic resonance imaging (MRI) and triphenyl tetrazolium chloride staining, and analyzed cardiac function by MRI and echocardiography. Results Transient LAD occlusions were found to increase EC proliferation and arteriole formation in the entire myocardium. These effects required β1 integrin on ECs, except for arteriole formation in the ischemic part of the myocardium. Furthermore, this integrin subunit was also relevant for basal and mechanically induced proliferation of human coronary artery ECs. Notably, β1 integrin was needed for cardioprotection induced by transient LAD occlusions, and the absence of endothelial β1 integrin resulted in impaired growth of blood vessels into the infarcted myocardium and reduced cardiac function after permanent LAD occlusion. Conclusion We showed that endothelial β1 integrin is required for adaptation of the heart to cardiac ischemia and protection from myocardial infarction.

scholarly journals Biofunctional Peptide FNIII14: Therapeutic Potential

Encyclopedia ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 350-359
Author(s):  
Motomichi Fujita ◽  
Manabu Sasada ◽  
Takuya Iyoda ◽  
Satoshi Osada ◽  
Hiroaki Kodama ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Extracellular Matrix ◽  
Conformational Changes ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Malignant Tumors ◽  
Β1 Integrin ◽  
Inactive Form ◽  
Functional Inactivation ◽  
Organ Fibrosis

Biofunctional peptide FNIII14, which is derived from the 14th fibronectin (FN) type III-like (FN-III) repeat of FN molecule, is capable of inhibiting cell adhesion to the extracellular matrix (ECM). This functional site is usually buried within the molecular structure of FN, but can be exposed by conformational changes and proteolytic cleavage. Peptide FNIII14 can induce a conformational change in β1-integrin from the active to the inactive form, causing functional inactivation. Based on this anti-adhesive activity, peptide FNIII14 exhibits therapeutic potential for several diseases such as metabolic diseases, organ fibrosis, and malignant tumors. Peptide FNIII14 blocks integrin-mediated signaling by a mechanism entirely distinct from that of conventional antagonisitic peptides, including Arg-Gly-Asp peptides that competitively inhibit the ECM binding of integrin.

Differences in phosphatase modulation of α4 β1 and α5 β1 integrin-mediated adhesion and migration of B16F1 cells

1999 ◽  
Vol 77 (5) ◽  
pp. 409-420 ◽  
Author(s):  
Dolores Hangan-Steinman ◽  
Wai-chi Ho ◽  
Priti Shenoy ◽  
Bosco MC Chan ◽  
Vincent L Morris
Keyword(s):  
Cell Adhesion ◽  
Adhesive Strength ◽  
Cell Movement ◽  
Protein Tyrosine Phosphatases ◽  
Β1 Integrin ◽  
Phosphatase Inhibitors ◽  
Β1 Integrins ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
B16f1 Cell

It is well established that a biphasic relationship exists between the adhesive strength of β1 integrins and their ability to mediate cell movement. Thus, cell movement increases progressively with adhesive strength, but beyond a certain point of optimal interaction, cell movement is reduced with further increases in adhesive function. The interplay between the various kinase and phosphatase activities provides the balance in β1 integrin-mediated cell adhesion and migration. In the present study, the significance of protein tyrosine phosphatases (PTP) and ser/thr protein phosphatases (PP) in α4β1 and α5β1 integrin-mediated mouse melanoma B16F1 cell anchorage and migration on fibronectin was characterized using phosphatase inhibitors. At low fibronectin concentration, α5β1 functioned as the predominant receptor for cell movement; a role for α4β1 in B16F1 cell migration increased progressively with fibronectin concentration. Treatment of B16F1 cells with PTP inhibitors, sodium orthovanadate (Na3VO4) and phenylarsine oxide (PAO), or PP-1/2A inhibitor, okadaic acid (OA), abolished cell movement. Inhibition of cell movement by PAO and OA was associated by a reduction in the adhesive strength of α4β1 and α5β1. In contrast, treatment of B16F1 cells with Na3VO4 resulted in selective stimulation of the adhesive function of α5β1, but not α4β1. Therefore, our results demonstrate that (i) both PTP and PP-1/2A have roles in cell movement, (ii) modulation of cell movement by PTP and PP-1/2A may involve either a stimulation or reduction of β1 integrin adhesive strength, and (iii) distinct phosphatase-mediated signaling pathways for differential regulation of the various β1 integrins exist. Key words: phosphatases, integrins, cell movement, cell adhesion.

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