A Novel Actin Barbed-End-Capping Activity in EPS-8 Regulates Apical Morphogenesis in Intestinal Cells of Caenorhabditis Elegans

Nat Cell Biol. 2004 Dec;6(12):1173-9. doi: 10.1038/ncb1198. Epub 2004 Nov 21.

Abstract

Redundant gene function frequently hampers investigations of the physiological roles of mammalian proteins. This is the case for Eps8, a receptor tyrosine kinase (RTK) substrate that participates in the activation of the Rac-specific guanine nucleotide-exchange function of Sos1 (refs 2-5), thereby regulating actin remodelling by RTKs. EPS8-knockout mice, however, exhibit no evident phenotype, owing to the redundant function of three other EPS8-related genes. Here we show that in the nematode Caenorhabditis elegans, only one orthologue of the EPS8 gene exists, which gives rise to two alternatively spliced isoforms, EPS-8A and EPS-8B, differing at their carboxyl termini. In the nematode, eps-8 is essential for embryonic development. Furthermore, EPS-8A, but not EPS-8B, is specifically required for proper apical morphogenesis in the intestinal cells. This latter phenotype could be precisely correlated with a previously unknown actin barbed-end-capping activity, which is present in the C terminus of the EPS-8A isoform. Therefore, nematode genetics allowed not only the unmasking of distinct EPS-8-linked phenotypes, but also the definition of a novel function for this molecule in actin dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure
  • Actins / biosynthesis*
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / isolation & purification
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / metabolism*
  • Cytoskeletal Proteins
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • Epithelial Cells / metabolism
  • Epithelial Cells / ultrastructure
  • Intestinal Mucosa / metabolism
  • Intestines / embryology*
  • Intestines / ultrastructure
  • Microscopy, Electron, Transmission
  • Microvilli / metabolism
  • Microvilli / ultrastructure
  • Molecular Sequence Data
  • Organogenesis / physiology*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary / genetics
  • Proteins / genetics
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cytoskeletal Proteins
  • DNA, Complementary
  • EPS-8 protein, C elegans
  • Eps8 protein, mouse
  • Protein Isoforms
  • Proteins

Associated data

  • GENBANK/AY611484
  • GENBANK/AY611485