Epidermal morphogenesis is responsible for the change in shape of the C. elegans embryo from an ovoid into a worm, and involves two cadherin dependent-events: ventral enclosure and elongation. We have previously shown that animals homozygous for a alpha-catenin mutation
hmp-1(
fe4) provide a sensitive background to identify molecules that contribute to cadherin-catenin complex function [1]. These primary results have provided the rationale for a genome-wide RNAi screen for C. elegans genes whose loss-of-function enhances the
fe4 phenotype [2]. Our group has recently completed the screen of Chromosome II and III from which we have identified a number of genes that contribute to the regulation of actin dynamics. We are particularly interested in one of these genes, which encodes the C. elegans zyxin homologue.
hmp-1(
fe4);
zyx-1(RNAi) embryos show 100%; lethality and arrest with severe elongation defects. Two mutants for
zyx-1 are available: like
zyx-1(RNAi), both
zyx-1(
um4) and
zyx-1(
gk442)enhance the
hmp-1(
fe4) phenotype.
zyx-1(
um4) is a deletion that removes the LIM domain from the zyxin protein.
zyx-1(
gk442) is a predicted null mutation, and homozygotes for the mutation display a sterile and skinny phenotype, although it is yet unclear whether the sterility is caused by the
zyx-1 loss of function itself or by a linked mutation affecting another gene. Zyxin has long been known to be present at focal adhesions and it has also been shown to be present at cadherin-based junctions in cell culture experiments [3]. Our data provide the first evidence of a role for zyxin at adherens junction in an in vivo model. Zyxin has also been shown to interact with alpha-actinin and Ena/VASP suggesting a role in the regulation of actin remodelling [4]. We are currently attempting to determine the mechanistic basis of the zyxin-a-catenin interaction. 1.Pettitt, J., et al., The Caenorhabditis elegans
p120 catenin homologue, JAC-1, modulates cadherin-catenin function during epidermal morphogenesis. J Cell Biol, 2003. 162(1): p. 15-22. 2.Cox, E.A. and J. Hardin. A feeding RNAi screen reveals novel regulators of cadherin-mediated adhesion during morphogenesis, including the tropomodulin homolog, TMD-1. in 15th International worm meeting. 2005. Los Angeles. 3.Hansen, M.D. and M.C. Beckerle, Opposing roles of zyxin/LPP ACTA repeats and the LIM domain region in cell-cell adhesion. J Biol Chem, 2006. 281(23): p. 16178-88. 4.Hoffman, L.M., et al., Genetic ablation of zyxin causes Mena/VASP mislocalization, increased motility, and deficits in actin remodeling. J Cell Biol, 2006. 172(5): p. 771-82.