scholarly journals Role of β1 integrin in thrombocytopoiesis

2021 ◽  
Vol 10 ◽  
Author(s):  
Maria Mazzarini ◽  
Paola Verachi ◽  
Fabrizio Martelli ◽  
Anna Rita Migliaccio
Keyword(s):  
Β1 Integrin

scholarly journals Receptor-Specific Mechanisms Regulate Phosphorylation of AKT at Ser473: Role of RICTOR in β1 Integrin-Mediated Cell Survival

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e32081 ◽  
Author(s):  
Anjum Riaz ◽  
Kathrin Stephanie Zeller ◽  
Staffan Johansson
Keyword(s):  
Cell Survival ◽  
Β1 Integrin

scholarly journals The mechano-sensitive response of β1 integrin promotes SRC-positive late endosome recycling and activation of Yes-associated protein

2020 ◽  
Vol 295 (39) ◽  
pp. 13474-13487
Author(s):  
Marc R. Block ◽  
Molly Brunner ◽  
Théo Ziegelmeyer ◽  
Dominique Lallemand ◽  
Mylène Pezet ◽  
...  
Keyword(s):  
Late Endosome ◽  
Cell Periphery ◽  
Β1 Integrin ◽  
Nonreceptor Tyrosine Kinase ◽  
Cell Contractility ◽  
Late Endosomes ◽  
Important Regulator ◽  
Nuclear Shuttling ◽  
Endosomal System

Yes-associated protein (YAP) signaling has emerged as a crucial pathway in several normal and pathological processes. Although the main upstream effectors that regulate its activity have been extensively studied, the role of the endosomal system has been far less characterized. Here, we identified the late endosomal/lysosomal adaptor MAPK and mTOR activator (LAMTOR) complex as an important regulator of YAP signaling in a preosteoblast cell line. We found that p18/LAMTOR1-mediated peripheral positioning of late endosomes allows delivery of SRC proto-oncogene, nonreceptor tyrosine kinase (SRC) to the plasma membrane and promotes activation of an SRC-dependent signaling cascade that controls YAP nuclear shuttling. Moreover, β1 integrin engagement and mechano-sensitive cues, such as external stiffness and related cell contractility, controlled LAMTOR targeting to the cell periphery and thereby late endosome recycling and had a major impact on YAP signaling. Our findings identify the late endosome recycling pathway as a key mechanism that controls YAP activity and explains YAP mechano-sensitivity.

Role of the β1-integrin cytoplasmic tail in mediating invasin-promoted internalization of Yersinia

2002 ◽  
Vol 115 (13) ◽  
pp. 2669-2678 ◽  
Author(s):  
Anna Gustavsson ◽  
Annika Armulik ◽  
Cord Brakebusch ◽  
Reinhard Fässler ◽  
Staffan Johansson ◽  
...  
Keyword(s):  
Marked Reduction ◽  
Yersinia Pseudotuberculosis ◽  
Host Cells ◽  
Β1 Integrin ◽  
Complex Structures ◽  
Wild Type ◽  
Similar Reduction ◽  
Focal Complex ◽  
Β1 Integrins

Invasin of Yersinia pseudotuberculosis binds to β1-integrins on host cells and triggers internalization of the bacterium. To elucidate the mechanism behind the β1-integrin-mediated internalization of Yersinia, a β1-integrin-deficient cell line, GD25, transfected with wild-type β1A, β1B or different mutants of the β1A subunit was used. Both β1A and β1B bound to invasin-expressing bacteria, but only β1A was able to mediate internalization of the bacteria. The cytoplasmic region of β1A, differing from β1B, contains two NPXY motifs surrounding a double threonine site. Exchanging the tyrosines of the two NPXYs to phenylalanines did not inhibit the uptake, whereas a marked reduction was seen when the first tyrosine (Y783) was exchanged to alanine. A similar reduction was seen when the two nearby threonines (TT788-9) were exchanged with alanines. It was also noted that cells affected in bacterial internalization exhibited reduced spreading capability when seeded onto invasin, suggesting a correlation between the internalization of invasin-expressing bacteria and invasin-induced spreading. Likewise, integrins defective in forming peripheral focal complex structures was unable to mediate uptake of invasin-expressing bacteria.

scholarly journals Talin is required for integrin-mediated platelet function in hemostasis and thrombosis

2007 ◽  
Vol 204 (13) ◽  
pp. 3103-3111 ◽  
Author(s):  
Brian G. Petrich ◽  
Patrizia Marchese ◽  
Zaverio M. Ruggeri ◽  
Saskia Spiess ◽  
Rachel A.M. Weichert ◽  
...  
Keyword(s):  
Platelet Adhesion ◽  
Ex Vivo ◽  
Focal Adhesions ◽  
Β1 Integrin ◽  
Normal Morphology ◽  
And Function ◽  
Specific Deletion

Integrins are critical for hemostasis and thrombosis because they mediate both platelet adhesion and aggregation. Talin is an integrin-binding cytoplasmic adaptor that is a central organizer of focal adhesions, and loss of talin phenocopies integrin deletion in Drosophila. Here, we have examined the role of talin in mammalian integrin function in vivo by selectively disrupting the talin1 gene in mouse platelet precursor megakaryocytes. Talin null megakaryocytes produced circulating platelets that exhibited normal morphology yet manifested profoundly impaired hemostatic function. Specifically, platelet-specific deletion of talin1 led to spontaneous hemorrhage and pathological bleeding. Ex vivo and in vitro studies revealed that loss of talin1 resulted in dramatically impaired integrin αIIbβ3-mediated platelet aggregation and β1 integrin–mediated platelet adhesion. Furthermore, loss of talin1 strongly inhibited the activation of platelet β1 and β3 integrins in response to platelet agonists. These data establish that platelet talin plays a crucial role in hemostasis and provide the first proof that talin is required for the activation and function of mammalian α2β1 and αIIbβ3 integrins in vivo.

scholarly journals Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and β1-integrin function

2018 ◽  
Vol 115 (41) ◽  
pp. E9630-E9639 ◽  
Author(s):  
Virginia Andreani ◽  
Senthilkumar Ramamoorthy ◽  
Abhinav Pandey ◽  
Ekaterina Lupar ◽  
Stephen L. Nutt ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
Plasma Cell ◽  
Target Genes ◽  
Β1 Integrin ◽  
Plasma Cell Differentiation ◽  
And Migration ◽  
And Function ◽  
Antibody Secreting Cells

Plasma cell differentiation involves coordinated changes in gene expression and functional properties of B cells. Here, we study the role of Mzb1, a Grp94 cochaperone that is expressed in marginal zone (MZ) B cells and during the terminal differentiation of B cells to antibody-secreting cells. By analyzing Mzb1−/−Prdm1+/gfp mice, we find that Mzb1 is specifically required for the differentiation and function of antibody-secreting cells in a T cell-independent immune response. We find that Mzb1-deficiency mimics, in part, the phenotype of Blimp1 deficiency, including the impaired secretion of IgM and the deregulation of Blimp1 target genes. In addition, we find that Mzb1−/− plasmablasts show a reduced activation of β1-integrin, which contributes to the impaired plasmablast differentiation and migration of antibody-secreting cells to the bone marrow. Thus, Mzb1 function is required for multiple aspects of plasma cell differentiation.

scholarly journals Gelsolin Mediates Collagen Phagocytosis through a Rac-dependent Step

2004 ◽  
Vol 15 (2) ◽  
pp. 588-599 ◽  
Author(s):  
Pamela D. Arora ◽  
Michael Glogauer ◽  
Andras Kapus ◽  
David J. Kwiatkowski ◽  
Christopher A. McCulloch
Keyword(s):  
Actin Filaments ◽  
Calcium Ionophore ◽  
Initial Contact ◽  
Β1 Integrin ◽  
Wild Type ◽  
Collagen Binding ◽  
Calcium Dependent ◽  
Collagen Phagocytosis ◽  
Α2β1 Integrin

The role of gelsolin, a calcium-dependent actin-severing protein, in mediating collagen phagocytosis, is not defined. We examined α2β1 integrin-mediated phagocytosis in fibroblasts from wild-type (WT) and gelsolin knockout (Gsn-) mice. After initial contact with collagen beads, collagen binding and internalization were 60% lower in Gsn- than WT cells. This deficiency was restored by transfection with gelsolin or with β1 integrin-activating antibodies. WT cells showed robust rac activation and increased [Ca2+]i during early contact with collagen beads, but Gsn- cells showed very limited responses. Transfected gelsolin in Gsn- cells restored rac activation after collagen binding. Transfection of Gsn- cells with active rac increased collagen binding to WT levels. Chelation of intracellular calcium inhibited collagen binding and rac activation, whereas calcium ionophore induced rac activation in WT and Gsn- cells. We conclude that the ability of gelsolin to remodel actin filaments is important for collagen-induced calcium entry; calcium in turn is required for rac activation, which subsequently enhances collagen binding to unoccupied α2β1 integrins.

scholarly journals Tetraspanin 3, as a Novel Regulator of Intracellular β1 Integrin Recycling, Promotes Non-Small Cell Lung Cancer Cell Proliferation

2021 ◽  
Author(s):  
Hongbo Su ◽  
Yitong Xu ◽  
Yao Zhang ◽  
Xizi Jiang ◽  
Qingfu Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Β1 Integrin ◽  
Small Cell Lung ◽  
Nsclc Tissue ◽  
Tumor Node Metastasis Stage

Abstract Background: The role of tetraspanins in cancer development has been widely reported. However, the expression and roles of tetraspanin 3 (TSPAN3) in solid tumors, including non-small cell lung cancer (NSCLC), have not yet been extensively investigated. In this study, we explored the role of TSPAN3 in NSCLC and its potential role in the trafficking of integrin β1, which is highly expressed in this type of cancer.Methods: The expression of TSPAN3 in NSCLC tissue and NSCLC cell lines was evaluated, and the correlation between TSPAN3 expression and disease progression was assessed. Furthermore, loss- and gain-of-expression studies were conducted to determine the biological function of TSPAN3 both in vivo and vitro. The regulatory role of TSPAN3 in β1 integrin expression and intracellular recycling was studied through western blot, RT-PCR, and immunofluorescence analyses.Results: TSPAN3 was found to be highly expressed in lung cancer cells and tissues. Moreover, high levels of TSPAN3 positively correlated with poor differentiation, lymph node involvement, advanced pathological tumor-node-metastasis stage, and poor prognosis in NSCLC patients. TSPAN3 showed the potential to promote the proliferation of NSCLC cells in vitro and in vivo. Specifically, TSPAN3 was found to interact with β1 integrin and Rab11a, thereby facilitating the sorting of β1 integrin into Rab11a endosomes and promoting β1 integrin recycling and upregulation. Conclusions: These findings reveal a novel role for TSPAN3 in the regulation of intracellular recycling of β1 integrin. Hence, TSPAN3 may represent a potentially valuable therapeutic target for NSCLC.

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