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First published online 20 October 2009
doi: 10.1242/jcs.031948
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Research Article |
-catenin is essential in early embryogenesis and is functionally linked to cadherins and small GTPases
1 Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
2 Program in Genes and Development, University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA
3 Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA
4 Department of Anatomy and Cell Biology, The Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
* Author for correspondence (pdmccrea{at}mdanderson.org)
Accepted 2 September 2009
Catenins of the p120 subclass display an array of intracellular localizations and functions. Although the genetic knockout of mouse
-catenin results in mild cognitive dysfunction, we found severe effects of its depletion in Xenopus.
-catenin in Xenopus is transcribed as a full-length mRNA, or as three (or more) alternatively spliced isoforms designated A, B and C. Further structural and functional complexity is suggested by three predicted and alternative translation initiation sites. Transcript analysis suggests that each splice isoform is expressed during embryogenesis, with the B and C transcript levels varying according to developmental stage. Unlike the primarily neural expression of
-catenin reported in mammals,
-catenin is detectable in most adult Xenopus tissues, although it is enriched in neural structures.
-catenin associates with classical cadherins, with crude embryo fractionations further revealing non-plasma-membrane pools that might be involved in cytoplasmic and/or nuclear functions. Depletion of
-catenin caused gastrulation defects, phenotypes that were further enhanced by co-depletion of the related p120-catenin. Depletion was significantly rescued by titrated p120-catenin expression, suggesting that these catenins have shared roles. Biochemical assays indicated that
-catenin depletion results in reduced cadherin levels and cell adhesion, as well as perturbation of RhoA and Rac1. Titrated doses of C-cadherin, dominant-negative RhoA or constitutively active Rac1 significantly rescued
-catenin depletion. Collectively, our experiments indicate that
-catenin has an essential role in amphibian development, and has functional links to cadherins and Rho-family GTPases.
Key words: Gastrulation, Rho, Rac
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