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First published online 23 April 2003
doi: 10.1242/jcs.00445


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Journal of Cell Science 116, 2333-2343 (2003)
doi: 10.1242/jcs.00445


Research Article

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

Jie Na, Mungo Marsden and Douglas W. DeSimone*

Department of Cell Biology, University of Virginia School of Medicine, PO Box 800732, Charlottesville, VA 22908, USA

* Author for correspondence (e-mail: desimone{at}virginia.edu)

Accepted 27 February 2003

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 {alpha}4 constructs and {alpha}4-ectodomain/{alpha}-cytoplasmic tail chimeras were generated and expressed in whole embryos. Normal gastrula cells lack integrin {alpha}4 and, correspondingly, are unable to adhere to the {alpha}4 ligand, the V-region of FN. The ability of {alpha}4 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 {alpha}4 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.

Key words: Integrin, Cell migration, Cell adhesion, Xenopus, Fibronectin


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