scholarly journals Recreation of the terminal events in physiological integrin activation

2010 ◽  
Vol 188 (1) ◽  
pp. 157-173 ◽  
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.

Amygdalin Modulates Prostate Cancer Cell Adhesion and Migration In Vitro

2019 ◽  
Vol 72 (3) ◽  
pp. 528-537 ◽  
Author(s):  
Jens Mani ◽  
Jens Neuschäfer ◽  
Christian Resch ◽  
Jochen Rutz ◽  
Sebastian Maxeiner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Adhesion ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Adhesion ◽  
Cell Adhesion And Migration ◽  
And Migration

scholarly journals Neural crest cell migration: requirements for exogenous fibronectin and high cell density.

1983 ◽  
Vol 96 (2) ◽  
pp. 462-473 ◽  
Author(s):  
R A Rovasio ◽  
A Delouvee ◽  
K M Yamada ◽  
R Timpl ◽  
J P Thiery
Keyword(s):  
Cell Adhesion ◽  
Neural Crest ◽  
Type I Collagen ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Type I ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
Crest Cell

Cells of the neural crest participate in a major class of cell migratory events during embryonic development. From indirect evidence, it has been suggested that fibronectin (FN) might be involved in these events. We have directly tested the role of FN in neural crest cell adhesion and migration using several in vitro model systems. Avian trunk neural crest cells adhered readily to purified plasma FN substrates and to extracellular matrices containing cellular FN. Their adhesion was inhibited by antibodies to a cell-binding fragment of FN. In contrast, these cells did not adhere to glass, type I collagen, or to bovine serum albumin in the absence of FN. Neural crest cell adhesion to laminin (LN) was significantly less than to FN; however, culturing of crest cells under conditions producing an epithelioid phenotype resulted in cells that could bind equally as well to LN as to FN. The migration of neural crest cells appeared to depend on both the substrate and the extent of cell interactions. Cells migrated substantially more rapidly on FN than on LN or type I collagen substrates; if provided a choice between stripes of FN and glass or LN, cells migrated preferentially on the FN. Migration was inhibited by antibodies against the cell-binding region of FN, and the inhibition could be reversed by a subsequent addition of exogenous FN. However, the migration on FN was random and displayed little persistence of direction unless cells were at high densities that permitted frequent contacts. The in vitro rate of migration of cells on FN-containing matrices was 50 microns/h, similar to their migration rates along the narrow regions of FN-containing extracellular matrix in migratory pathways in vivo. These results indicate that FN is important for neural crest cell adhesion and migration and that the high cell densities of neural crest cells in the transient, narrow migratory pathways found in the embryo are necessary for effective directional migration.

Improving Fluorescence-Based Assays for the In Vitro Analysis of Cell Adhesion and Migration

2002 ◽  
Vol 20 (3) ◽  
pp. 285-304 ◽  
Author(s):  
Paola Spessotto ◽  
Emiliana Giacomello ◽  
Roberto Perris
Keyword(s):  
Cell Adhesion ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
Vitro Analysis ◽  
In Vitro Analysis

Fluorescence-Based Assays for In Vitro Analysis of Cell Adhesion and Migration

2009 ◽  
pp. 221-250 ◽  
Author(s):  
Paola Spessotto ◽  
Katia Lacrima ◽  
Pier Andrea Nicolosi ◽  
Eliana Pivetta ◽  
Martina Scapolan ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
Vitro Analysis ◽  
In Vitro Analysis

Role of the docking protein Gab2 in β1-integrin signaling pathway-mediated hematopoietic cell adhesion and migration

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2351-2359 ◽  
Author(s):  
Wen-Mei Yu ◽  
Teresa S. Hawley ◽  
Robert G. Hawley ◽  
Cheng-Kui Qu
Keyword(s):  
Cell Adhesion ◽  
Signaling Pathway ◽  
Hematopoietic Cell ◽  
Integrin Signaling ◽  
Pleckstrin Homology Domain ◽  
Β1 Integrin ◽  
Kinase Activation ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
Docking Protein

Gab2, a newly identified pleckstrin homology domain-containing docking protein, is a major binding protein of SHP-2 tyrosine phosphatase in interleukin (IL)-3–stimulated hematopoietic cells. Its signaling mechanism remains largely unknown. We report here an important regulatory role for Gab2 in β1 integrin signaling pathway that mediates hematopoietic cell adhesion and migration. Cross-linking of the β1 integrin on Ba/F3 cells induced rapid tyrosine phosphorylation of Gab2 and its association with Syk kinase, SHP-2 phosphatase, and the p85 subunit of phosphatidylinositol (PI)-3 kinase. In addition, Gab2 was also constitutively associated with SHP-1 phosphatase via its C-terminal Src homology 2 domain. Overexpression of the pleckstrin homology domain or a mutant Gab2 molecule lacking SHP-2 binding sites resulted in significant reductions in Ba/F3 cell adhesion and migration. Biochemical analyses revealed that enforced expression of Gab2 mutant molecules dramatically reduced β1-integrin ligation-triggered PI3 kinase activation, whereas Erk kinase activation remained unaltered. Furthermore, transduction of primary hematopoietic progenitor cells from viable motheaten mice with these mutant Gab2 molecules also significantly ameliorated their enhanced migration capacity associated with theSHP1 gene mutation. Taken together, these results suggest an important signaling role for Gab2 in regulating hematopoietic cell adhesion and migration.

scholarly journals Protein Kinase Cδ-Mediated Phosphorylation of Phospholipase D Controls Integrin-Mediated Cell Spreading

2010 ◽  
Vol 30 (21) ◽  
pp. 5086-5098 ◽  
Author(s):  
Young Chan Chae ◽  
Kyung Lock Kim ◽  
Sang Hoon Ha ◽  
Jaeyoon Kim ◽  
Pann-Ghill Suh ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Protein Kinase ◽  
Phospholipase D ◽  
Molecular Mechanisms ◽  
Cell Spreading ◽  
Integrin Signaling ◽  
Integrin Activation ◽  
Actin Remodeling ◽  
And Migration ◽  
Protein Kinase Cδ

ABSTRACT Integrin signaling plays critical roles in cell adhesion, spreading, and migration, and it is generally accepted that to regulate these integrin functions accurately, localized actin remodeling is required. However, the molecular mechanisms that control the targeting of actin regulation molecules to the proper sites are unknown. We previously demonstrated that integrin-mediated cell spreading and migration on fibronectin are dependent on the localized activation of phospholipase D (PLD). However, the mechanism underlying PLD activation by integrin is largely unknown. Here we demonstrate that protein kinase Cδ (PKCδ) is required for integrin-mediated PLD signaling. After integrin stimulation, PKCδ is activated and translocated to the edges of lamellipodia, where it colocalizes with PLD2. The abrogation of PKCδ activity inhibited integrin-induced PLD activation and cell spreading. Finally, we show that Thr566 of PLD2 is directly phosphorylated by PKCδ and that PLD2 mutation in this region prevents PLD2 activation, PLD2 translocation to the edge of lamellipodia, Rac translocation, and cell spreading after integrin activation. Together, these results suggest that PKCδ is a primary regulator of integrin-mediated PLD activation via the direct phosphorylation of PLD, which is essential for directing integrin-induced cell spreading.

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