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

• Published in: eLife 2017-08, Vol.6
• Main Authors: Li, Hanqing, Watson, Ash, Olechwier, Agnieszka, Anaya, Michael, Sorooshyari, Siamak K, Harnett, Dermott P, Lee, Hyung-Kook Peter, Vielmetter, Jost, Fares, Mario A, Garcia, K Christopher, Özkan, Engin, Labrador, Juan-Pablo, Zinn, Kai
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - chemistry; Antineoplastic agents; Axon guidance; Biological Assay; Biology; Bonds (Securities); Breast cancer; Cell surface; Computational Biology; Deconstruction; Displays (Marketing); Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila melanogaster - ultrastructure; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Embryo, Nonmammalian; Fluorescent Dyes - chemistry; Fruit flies (Tephritidae); Gene Expression Regulation, Developmental; Genes; Genomics; Growth cones; Growth Cones - metabolism; Growth Cones - ultrastructure; Identification cards; Identity; immunglobulin superfamily; Immunoglobulins; Insects; interactome; Membrane Proteins - genetics; Membrane Proteins - metabolism; Methods; motor axon guidance; motor neuron; Motor neurons; Motor Neurons - metabolism; Motor Neurons - ultrastructure; Muscles - metabolism; Muscles - ultrastructure; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nerves; Nervous System - growth & development; Nervous System - metabolism; Nervous System - ultrastructure; neural development; Neuromuscular system; Neurons; Neuroscience; Phycoerythrin - chemistry; Phylogeny; Protein binding; Protein Interaction Mapping - methods; Protein Isoforms - genetics; Protein Isoforms - metabolism; protein-protein interaction; Proteins; Signal Transduction; Surface plasmon resonance; Surface science
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.28111

An 'interactome' screen of all 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 and genes suggest that Beats are neuronal receptors for Sides expressed on peripheral tissues. 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. genes, encoding Side-VI receptors, are expressed in ISNb and ISN motor neurons.