Xenopus delta-catenin is essential in early embryogenesis and is functionally linked to cadherins and small GTPases

J Cell Sci. 2009 Nov 15;122(Pt 22):4049-61. doi: 10.1242/jcs.031948. Epub 2009 Oct 20.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alternative Splicing
  • Animals
  • Base Sequence
  • Cadherins / metabolism*
  • Catenins / genetics*
  • Catenins / metabolism*
  • Cell Adhesion
  • Delta Catenin
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism
  • Gastrula / metabolism*
  • Gastrula / ultrastructure
  • Gastrulation / physiology
  • Gene Knockout Techniques
  • Molecular Sequence Data
  • Neurulation / physiology
  • Xenopus laevis / embryology*
  • Xenopus laevis / metabolism
  • rac1 GTP-Binding Protein / metabolism*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Cadherins
  • Catenins
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein
  • Delta Catenin