Differential regulation of cell adhesive functions by integrin αsubunit cytoplasmic tails in vivo

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Abstract
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 α cytoplasmic tail in the specification of these developmentally significant adhesive functions. Cytoplasmic tail-deleted α4 constructs andα 4-ectodomain/α-cytoplasmic tail chimeras were generated and expressed in whole embryos. Normal gastrula cells lack integrin α4 and, correspondingly, are unable to adhere to the α4 ligand, the V-region of FN. The ability of α4 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 α4 cytoplasmic domain deletion mutant andα -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 specificα subunit tail sequences. These data suggest that α cytoplasmic tail signaling and changes in integrin activation state can regulate a variety of developmentally significant adhesive behaviors in both space and time.