During cell migration, the physical link between the extracellular substrate and the actin cytoskeleton mediated by receptors of the integrin family is constantly modified. We analyzed the mechanisms that regulate the clustering and incorporation of activated alphavbeta3 integrins into focal adhesions. Manganese (Mn2+) or mutational activation of integrins induced the formation of de novo F-actin-independent integrin clusters. These clusters recruited talin, but not other focal adhesion adapters, and overexpression of the integrin-binding head domain of talin increased clustering. Integrin clustering required immobilized ligand and was prevented by the sequestration of phosphoinositole-4,5-bisphosphate (PI(4,5)P2). Fluorescence recovery after photobleaching analysis of Mn(2+)-induced integrin clusters revealed increased integrin turnover compared with mature focal contacts, whereas stabilization of the open conformation of the integrin ectodomain by mutagenesis reduced integrin turnover in focal contacts. Thus, integrin clustering requires the formation of the ternary complex consisting of activated integrins, immobilized ligands, talin, and PI(4,5)P2. The dynamic remodeling of this ternary complex controls cell motility.
Accumulation of talin in nodes at the edge of the lamellipodium and separate incorporation into adhesion plaques at focal contacts in fibroblasts
A beta 3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation
Integrin alphaIIb beta3 reconstituted into lipid bilayers is nonclustered in its activated state but clusters after fibrinogen binding
Peptide-specific antibodies localize the major lipid binding sites of talin dimers to oppositely arranged N-terminal 47 kDa subdomains
Disruption of the talin gene compromises focal adhesion assembly in undifferentiated but not differentiated embryonic stem cells
Mechanisms and consequences of affinity modulation of integrin alpha(V)beta(3) detected with a novel patch-engineered monovalent ligand.
Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation
GAP43, MARCKS, and CAP23 modulate PI(4,5)P(2) at plasmalemmal rafts, and regulate cell cortex actin dynamics through a common mechanism
Conformation, localization, and integrin binding of talin depend on its interaction with phosphoinositides
Marching at the front and dragging behind: differential alphaVbeta3-integrin turnover regulates focal adhesion behavior
Crystal structure of the extracellular segment of integrin alpha Vbeta3 in complex with an Arg-Gly-Asp ligand
Integrin activation involves a conformational change in the alpha 1 helix of the beta subunit A-domain
A structural mechanism of integrin alpha(IIb)beta(3) "inside-out" activation as regulated by its cytoplasmic face
Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling
Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin
Microcontact printing of novel co-polymers in combination with proteins for cell-biological applications
Stabilizing the open conformation of the integrin headpiece with a glycan wedge increases affinity for ligand
RGD-grafted poly-L-lysine-graft-(polyethylene glycol) copolymers block non-specific protein adsorption while promoting cell adhesion
Phosphatidylinositol phosphate kinase type 1gamma and beta1-integrin cytoplasmic domain bind to the same region in the talin FERM domain
RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1
Spatial restriction of alpha4 integrin phosphorylation regulates lamellipodial stability and alpha4beta1-dependent cell migration
Membrane cholesterol, lateral mobility, and the phosphatidylinositol 4,5-bisphosphate-dependent organization of cell actin
The relative influence of metal ion binding sites in the I-like domain and the interface with the hybrid domain on rolling and firm adhesion by integrin alpha4beta7
An interaction between integrin and the talin FERM domain mediates integrin activation but not linkage to the cytoskeleton
β3 integrin interacts directly with GluA2 AMPA receptor subunit and regulates AMPA receptor expression in hippocampal neurons.
Integrin-dependent force transmission to the extracellular matrix by α-actinin triggers adhesion maturation
Integrin alphaIIbbeta3 activation in Chinese hamster ovary cells and platelets increases clustering rather than affinity.
Kindlin-3 mediates integrin αLβ2 outside-in signaling, and it interacts with scaffold protein receptor for activated-C kinase 1 (RACK1).
Galectin-3- and phospho-caveolin-1-dependent outside-in integrin signaling mediates the EGF motogenic response in mammary cancer cells
Altered expression pattern of integrin alphavbeta3 correlates with actin cytoskeleton in primary cultures of human breast cancer.
Probabilistic modeling and analysis of the effects of extra-cellular matrix density on the sizes, shapes, and locations of integrin clusters in adherent cells.
3D patterned agarose hydrogels for investigation of precursor cells in differentiation and chemoattraction
Targeting efficiency of RGD-modified nanocarriers with different ligand intervals in response to integrin αvβ3 clustering
Talin-bound NPLY motif recruits integrin-signaling adapters to regulate cell spreading and mechanosensing
Clustering of alpha(5)beta(1) integrins determines adhesion strength whereas alpha(v)beta(3) and talin enable mechanotransduction.
Peptides derived from central turn motifs within integrin αIIb and αV cytoplasmic tails inhibit integrin activation
Transmembrane and cytoplasmic domains in integrin activation and protein-protein interactions (review).
Cell adaptive response to extracellular matrix density is controlled by ICAP-1-dependent beta1-integrin affinity.
Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.
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