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

• Main Authors: Hanqing Li, Ash Watson, Agnieszka Olechwier, Michael Anaya, Siamak K Sorooshyari, Dermott P Harnett, Hyung-Kook (Peter) Lee, Jost Vielmetter, Mario A Fares, K Christopher Garcia, Engin Özkan, Juan-Pablo Labrador, Kai Zinn
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2017-08-01
• Series: eLife
• Subjects: protein-protein interaction; interactome; immunglobulin superfamily; neural development; motor neuron; motor axon guidance
• Online Access: https://elifesciences.org/articles/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.