Transmission of integrin β7 transmembrane domain topology enables gut lymphoid tissue development

Integrin activation regulates adhesion, extracellular matrix assembly, and cell migration, thereby playing an indispensable role in development and in many pathological processes. A proline mutation in the central integrin β3 transmembrane domain (TMD) creates a flexible kink that uncouples the topology of the inner half of the TMD from the outer half. In this study, using leukocyte integrin α4β7, which enables development of gut-associated lymphoid tissue (GALT), we examined the biological effect of such a proline mutation and report that it impairs agonist-induced talin-mediated activation of integrin α4β7, thereby inhibiting rolling lymphocyte arrest, a key step in transmigration. Furthermore, the α4β7(L721P) mutation blocks lymphocyte homing to and development of the GALT. These studies show that impairing the ability of an integrin β TMD to transmit talin-induced TMD topology inhibits agonist-induced physiological integrin activation and biological function in development.

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Establishment of substratum polarity in the blastocoel roof of the Xenopus embryo

Development ◽

10.1242/dev.126.9.1975 ◽

1999 ◽

Vol 126 (9) ◽

pp. 1975-1984 ◽

Cited By ~ 3

Author(s):

M. Nagel ◽

R. Winklbauer

Keyword(s):

Extracellular Matrix ◽

Cell Migration ◽

Signaling Pathways ◽

Fibril Formation ◽

Fgf Signaling ◽

Matrix Assembly ◽

Mesoderm Cell ◽

Guidance Cues ◽

Mesoderm Formation ◽

Fibronectin Fibrils

The fibronectin fibril matrix on the blastocoel roof of the Xenopus gastrula contains guidance cues that determine the direction of mesoderm cell migration. The underlying guidance-related polarity of the blastocoel roof is established in the late blastula under the influence of an instructive signal from the vegetal half of the embryo, in particular from the mesoderm. Formation of an oriented substratum depends on functional activin and FGF signaling pathways in the blastocoel roof. Besides being involved in tissue polarization, activin and FGF also affect fibronectin matrix assembly. Activin treatment of the blastocoel roof inhibits fibril formation, whereas FGF modulates the structure of the fibril network. The presence of intact fibronectin fibrils is permissive for directional mesoderm migration on the blastocoel roof extracellular matrix.

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Recreation of the terminal events in physiological integrin activation

The Journal of Cell Biology ◽

10.1083/jcb.200908045 ◽

2010 ◽

Vol 188 (1) ◽

pp. 157-173 ◽

Cited By ~ 186

Author(s):

Feng Ye ◽

Guiqing Hu ◽

Dianne Taylor ◽

Boris Ratnikov ◽

Andrey A. Bobkov ◽

...

Keyword(s):

Extracellular Matrix ◽

Cell Adhesion ◽

Integrin Signaling ◽

Integrin Activation ◽

Matrix Assembly ◽

Integrin Αiibβ3 ◽

Terminal Events ◽

Cell Adhesion And Migration ◽

And Migration

Increased affinity of integrins for the extracellular matrix (activation) regulates cell adhesion and migration, extracellular matrix assembly, and mechanotransduction. Major uncertainties concern the sufficiency of talin for activation, whether conformational change without clustering leads to activation, and whether mechanical force is required for molecular extension. Here, we reconstructed physiological integrin activation in vitro and used cellular, biochemical, biophysical, and ultrastructural analyses to show that talin binding is sufficient to activate integrin αIIbβ3. Furthermore, we synthesized nanodiscs, each bearing a single lipid-embedded integrin, and used them to show that talin activates unclustered integrins leading to molecular extension in the absence of force or other membrane proteins. Thus, we provide the first proof that talin binding is sufficient to activate and extend membrane-embedded integrin αIIbβ3, thereby resolving numerous controversies and enabling molecular analysis of reconstructed integrin signaling.

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Tensin links energy metabolism to extracellular matrix assembly

The Journal of Cell Biology ◽

10.1083/jcb.201702025 ◽

2017 ◽

Vol 216 (4) ◽

pp. 867-869 ◽

Cited By ~ 5

Author(s):

Emmanuel Dornier ◽

Jim C. Norman

Keyword(s):

Extracellular Matrix ◽

Cell Migration ◽

Energy Metabolism ◽

Protein Kinase ◽

Adenosine Monophosphate ◽

Matrix Assembly ◽

Cellular Processes ◽

Metabolic Sensor ◽

Fibrillar Adhesion ◽

Α5β1 Integrin

The regulation of integrin function is key to fundamental cellular processes, including cell migration and extracellular matrix (ECM) assembly. In this issue, Georgiadou et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201609066) report that the metabolic sensor adenosine monophosphate–activated protein kinase influences tensin production to regulate α5β1-integrin and fibrillar adhesion assembly and thus reveal an important connection between energy metabolism and ECM assembly.

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RSK2 Protein Suppresses Integrin Activation and Fibronectin Matrix Assembly and Promotes Cell Migration

Journal of Biological Chemistry ◽

10.1074/jbc.m112.423046 ◽

2012 ◽

Vol 287 (52) ◽

pp. 43424-43437 ◽

Cited By ~ 34

Author(s):

Joanna E. Gawecka ◽

Shirley S. Young-Robbins ◽

Florian J. Sulzmaier ◽

Maisel J. Caliva ◽

Minna M. Heikkilä ◽

...

Keyword(s):

Cell Migration ◽

Integrin Activation ◽

Matrix Assembly ◽

Fibronectin Matrix

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Neutrophil migration through in vitro interstitial matrix

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100124872 ◽

1992 ◽

Vol 50 (1) ◽

pp. 894-895

Author(s):

J. Roemer ◽

S.R. Simon

Keyword(s):

Extracellular Matrix ◽

Smooth Muscle ◽

Cell Migration ◽

Smooth Muscle Cells ◽

Inflammatory Cell ◽

Neutrophil Migration ◽

Culture Conditions ◽

Aortic Smooth Muscle ◽

Specific Culture

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.

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Faculty Opinions recommendation of The neural cell adhesion molecule L1 potentiates integrin-dependent cell migration to extracellular matrix proteins.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1009197.119458 ◽

2002 ◽

Author(s):

Genevieve Rougon

Keyword(s):

Extracellular Matrix ◽

Cell Migration ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Neural Cell Adhesion Molecule ◽

Matrix Proteins ◽

Neural Cell Adhesion ◽

Dependent Cell ◽

Cell Adhesion Molecule L1

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Faculty Opinions recommendation of Extracellular matrix stiffness and cell contractility control RNA localization to promote cell migration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.731988381.793541516 ◽

2018 ◽

Author(s):

Martin A Schwartz

Keyword(s):

Extracellular Matrix ◽

Cell Migration ◽

Rna Localization ◽

Matrix Stiffness ◽

Cell Contractility ◽

Promote Cell Migration ◽

Extracellular Matrix Stiffness

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Enhanced Piezoelectric Fibered Extracellular Matrix to Promote Cardiomyocyte Maturation and Tissue Formation: A 3D Computational Model

Biology ◽

10.3390/biology10020135 ◽

2021 ◽

Vol 10 (2) ◽

pp. 135

Author(s):

Pau Urdeitx ◽

Mohamed H. Doweidar

Keyword(s):

Extracellular Matrix ◽

Cell Migration ◽

Computational Models ◽

Cell Junctions ◽

Tissue Formation ◽

Cardiac Muscle Cells ◽

Cell Processes ◽

Electrical Stimuli ◽

Cell Cell

Mechanical and electrical stimuli play a key role in tissue formation, guiding cell processes such as cell migration, differentiation, maturation, and apoptosis. Monitoring and controlling these stimuli on in vitro experiments is not straightforward due to the coupling of these different stimuli. In addition, active and reciprocal cell–cell and cell–extracellular matrix interactions are essential to be considered during formation of complex tissue such as myocardial tissue. In this sense, computational models can offer new perspectives and key information on the cell microenvironment. Thus, we present a new computational 3D model, based on the Finite Element Method, where a complex extracellular matrix with piezoelectric properties interacts with cardiac muscle cells during the first steps of tissue formation. This model includes collective behavior and cell processes such as cell migration, maturation, differentiation, proliferation, and apoptosis. The model has employed to study the initial stages of in vitro cardiac aggregate formation, considering cell–cell junctions, under different extracellular matrix configurations. Three different cases have been purposed to evaluate cell behavior in fibered, mechanically stimulated fibered, and mechanically stimulated piezoelectric fibered extra-cellular matrix. In this last case, the cells are guided by the coupling of mechanical and electrical stimuli. Accordingly, the obtained results show the formation of more elongated groups and enhancement in cell proliferation.

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