Specific conserved C-terminal amino acids of Caenorhabditis elegans HMP-1/α-catenin modulate F-actin binding independently of vinculin

Stephanie L. Maiden, Neale Harrison, Jack Keegan, Brian Cain, Allison M. Lynch, Jonathan Pettitt, Jeff Hardin

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Stable intercellular adhesions formed through the cadherin-catenin complex are important determinants of proper tissue architecture and help maintain tissue integrity during morphogenetic movements in developing embryos. A key regulator of this stability is alpha-catenin, which connects the cadherin-catenin complex to the actin cytoskeleton. While the C- terminal F-actin-binding domain of alpha-catenin has been shown to be crucial for its function, a more detailed in vivo analysis of discrete regions and residues required for actin binding has not been performed. Using C. elegans as a model system, we have characterized mutations in hmp-1/alpha -catenin that identify HMP-1 residues 687-742 and 826-927, as well as amino acid 802, as critical to the localization of junctional proximal actin during epidermal morphogenesis. We also find that the S823F transition in a hypomorphic allele, hmp-1(fe4), decreases actin binding in vitro. Using hmp-1(fe4) animals in a mutagenesis screen, we were then able to identify eleven intragenic suppressors of hmp-1(fe4) that revert actin binding to wild-type levels. Using homology modeling, we show that these amino acids are positioned at key conserved sites within predicted a-helices in the C terminus. Through the use of transgenic animals, we also demonstrate that HMP-1 residues 315-494, which correspond to a putative mechanotransduction domain that binds vinculin in vertebrate alpha(E)-catenin, are not required during epidermal morphogenesis but may aid efficient recruitment of HMP-1 to the junction. Our studies are the first to identify key conserved amino acids in the C terminus of alpha-catenin that modulate F-actin binding in living embryos of a simple metazoan.

Original languageEnglish
Pages (from-to)5694-5706
Number of pages13
JournalThe Journal of Biological Chemistry
Volume288
Issue number8
Early online date27 Dec 2012
DOIs
Publication statusPublished - 22 Feb 2013

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Keywords

  • actin
  • adhesion
  • C. elegans
  • cadherins
  • morphogenesis
  • a-catenin
  • vinculin

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