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Title

Lateral mobility and nanoscale spatial arrangement of chemokine-activated α4β1 integrins on T cells

AuthorsSosa-Costa, Alberto; Isern de Val, Soledad; Sevilla-Movilla, Silvia; Borgman, Kyra J. E.; Manzo, Carlo; Teixidó, Joaquín ; Garcia-Parajo, Maria F.
KeywordsCell adhesion
Cell migration
Integrin
Membrane biophysics
Microscopy
Single particle analysis
Issue Date30-Sep-2016
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationThe Journal of Biological Chemistry 291 (40) 21053–21062 (2016)
AbstractChemokine stimulation of integrin α4β1-dependent T lymphocyte adhesion is a key step during lymphocyte trafficking. A central question regarding α4β1 function is how its lateral mobility and organization influence its affinity and avidity following cell stimulation with chemokines and/or ligands. Using single particle tracking and super-resolution imaging approaches, we explored the lateral mobility and spatial arrangement of individual α4β1 integrins on T cells exposed to different activating stimuli. We show that CXCL12 stimulation leads to rapid and transient α4β1 activation, measured by induction of the activation epitope recognized by the HUTS-21 anti-β1 antibody and by increased talin-β1 association. CXCL12-dependent α4β1 activation directly correlated with restricted lateral diffusion and integrin immobilization. Moreover, co-stimulation by CXCL12 together with soluble VCAM-1 potentiated integrin immobilization with a five-fold increase in immobile integrins as compared to unstimulated conditions. Our data indicate that docking by talin of the chemokine-activated α4β1 to the actin cytoskeleton favors integrin immobilization, which likely facilitates ligand interaction and increased adhesiveness. Super-resolution imaging showed that the nanoscale organization of high-affinity α4β1 remains unaffected following chemokine and/or ligand addition. Instead, newly activated α4β1 integrins organize on the cell membrane as independent units without joining pre-established integrin sites to contribute to cluster formation. Altogether, our results provide a rationale to understand how the spatiotemporal organization of activated α4β1 integrins regulates T lymphocyte adhesion.
Description11p.-8 fig.
Publisher version (URL)http://dx.doi.org/10.1074/jbc.M116.733709
URIhttp://hdl.handle.net/10261/154038
DOI10.1074/jbc.M116.733709
ISSN0021-9258
E-ISSN1083-351X
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