The Arf-GEF Schizo/Loner regulates N-cadherin to induce fusion competence of Drosophila myoblasts

Dev Biol. 2012 Aug 1;368(1):18-27. doi: 10.1016/j.ydbio.2012.04.031. Epub 2012 May 14.

Abstract

Myoblast fusion is a key process in multinucleated muscle formation. Prior to fusion, myoblasts recognize and adhere to each other with the aid of cell-adhesion proteins integrated into the membrane. Their intracellular domains participate in signal transduction by binding to cytoplasmic proteins. Here we identified the calcium-dependent cell-adhesion protein N-cadherin as the binding partner of the guanine-nucleotide exchange factor Schizo/Loner in Drosophila melanogaster. N-cadherin was expressed in founder cells and fusion-competent myoblasts of Drosophila during the first fusion phase. Our genetic analyses demonstrated that the myoblast fusion defect of schizo/loner mutants is rescued in part by the loss-of-function mutation of N-cadherin, which suggests that Schizo/Loner is a negative regulator of N-cadherin. Based on our findings, we propose a model where N-cadherin must be removed from the myoblast membrane to induce a protein-free zone at the cell-cell contact point to permit fusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factor 1 / genetics
  • ADP-Ribosylation Factor 1 / metabolism*
  • Animals
  • Animals, Genetically Modified
  • Binding Sites / genetics
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Fusion
  • Cell Line
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism
  • Female
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Immunohistochemistry
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Mutation
  • Myoblasts / cytology
  • Myoblasts / metabolism*
  • Protein Binding
  • Two-Hybrid System Techniques

Substances

  • CadN protein, Drosophila
  • Cadherins
  • Drosophila Proteins
  • Guanine Nucleotide Exchange Factors
  • Luminescent Proteins
  • Siz protein, Drosophila
  • ADP-Ribosylation Factor 1