Deconstruction of the beaten Path-Sidestep interaction network provides insights into neuromuscular system development

Elife. 2017 Aug 15:6:e28111. doi: 10.7554/eLife.28111.


An 'interactome' screen of all Drosophila cell-surface and secreted proteins containing immunoglobulin superfamily (IgSF) domains discovered a network formed by paralogs of Beaten Path (Beat) and Sidestep (Side), a ligand-receptor pair that is central to motor axon guidance. Here we describe a new method for interactome screening, the Bio-Plex Interactome Assay (BPIA), which allows identification of many interactions in a single sample. Using the BPIA, we 'deorphanized' four more members of the Beat-Side network. We confirmed interactions using surface plasmon resonance. The expression patterns of beat and side genes suggest that Beats are neuronal receptors for Sides expressed on peripheral tissues. side-VI is expressed in muscle fibers targeted by the ISNb nerve, as well as at growth cone choice points and synaptic targets for the ISN and TN nerves. beat-V genes, encoding Side-VI receptors, are expressed in ISNb and ISN motor neurons.

Keywords: D. melanogaster; immunglobulin superfamily; interactome; motor axon guidance; motor neuron; neural development; neuroscience; protein-protein interaction.

MeSH terms

  • Animals
  • Antibodies / chemistry
  • Biological Assay
  • Computational Biology
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism*
  • Drosophila melanogaster / ultrastructure
  • Embryo, Nonmammalian
  • Fluorescent Dyes / chemistry
  • Gene Expression Regulation, Developmental
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Motor Neurons / metabolism*
  • Motor Neurons / ultrastructure
  • Muscles / metabolism*
  • Muscles / ultrastructure
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Nervous System / growth & development
  • Nervous System / metabolism*
  • Nervous System / ultrastructure
  • Phycoerythrin / chemistry
  • Phylogeny
  • Protein Interaction Mapping / methods
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Signal Transduction


  • Antibodies
  • Drosophila Proteins
  • Fluorescent Dyes
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • beat-Ia protein, Drosophila
  • side protein, Drosophila
  • Phycoerythrin