期刊
JOURNAL OF CELL SCIENCE
卷 122, 期 22, 页码 4049-4061出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.031948
关键词
Gastrulation; Rho; Rac
类别
资金
- NIH [GM52112, CA111891]
- Anderson Cancer Center Institutional Research
- National Cancer Institute Core [CA-16672]
- DOD [PC040569]
Catenins of the p120 subclass display an array of intracellular localizations and functions. Although the genetic knockout of mouse delta-catenin results in mild cognitive dysfunction, we found severe effects of its depletion in Xenopus. delta-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 delta-catenin reported in mammals, delta-catenin is detectable in most adult Xenopus tissues, although it is enriched in neural structures. delta-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 delta-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 delta-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 delta-catenin depletion. Collectively, our experiments indicate that delta-catenin has an essential role in amphibian development, and has functional links to cadherins and Rho-family GTPases.
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