J Cell Sci 2003 Jun 01;116Pt 11:2333-43. doi: 10.1242/jcs.00445.

Differential regulation of cell adhesive functions by integrin alpha subunit cytoplasmic tails in vivo.

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Cell adhesion to fibronectin (FN) is crucial for early vertebrate morphogenesis. In Xenopus gastrulae, several distinct integrin-dependent adhesive behaviors can be identified: adhesion of cells to FN, assembly of FN fibrils, and initiation of cell spreading and migration in response to mesoderm inducing signals. We have taken a chimeric integrin approach to investigate the role of the integrin alpha cytoplasmic tail in the specification of these developmentally significant adhesive functions. Cytoplasmic tail-deleted alpha4 constructs and alpha4-ectodomain/alpha-cytoplasmic tail chimeras were generated and expressed in whole embryos. Normal gastrula cells lack integrin alpha4 and, correspondingly, are unable to adhere to the alpha4 ligand, the V-region of FN. The ability of alpha4 constructs to promote adhesive behaviors was established by placing tissue explants or dissociated cells on an FN V-region fusion protein that lacks the RGD (Arg-Gly-Asp)/synergy sites or treating whole embryos with antibodies that block endogenous integrin-FN interactions. We found that each alpha4 cytoplasmic domain deletion mutant and alpha-tail chimera examined could support cell attachment; however, activin induction-dependent cell spreading, mesoderm cell and explant motility, and the ability to assemble FN matrix on the blastocoel roof varied with specific alpha subunit tail sequences. These data suggest that alpha cytoplasmic tail signaling and changes in integrin activation state can regulate a variety of developmentally significant adhesive behaviors in both space and time.

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Species referenced: Xenopus laevis
Genes referenced: fn1
???displayArticle.antibodies??? Fn1 Ab1 Fn1 Ab10 Itgb1 Ab3