A Screen of Cell-Surface Molecules Identifies Leucine-Rich Repeat Proteins as Key Mediators of Synaptic Target Selection

• DOI: 10.1016/j.neuron.2008.07.037
• Publication Date: 2008-09-25T08:40:01Z
• Authors: Mitsuhiko Kurusu; Amy Cording; Misako Taniguchi; Kaushiki Menon; Emiko Suzuki; Kai Zinn
• Keywords: Repetitive Sequences, Amino Acid; 0301 basic medicine; 570; Neuroscience(all); Growth Cones; Models, Neurological; Muscle Fibers, Skeletal; BOUNDARY FORMATION; Neuromuscular Junction; DEVBIO; TARTAN; MOLNEURO; 03 medical and health sciences; Cell Movement; Leucine; FASCICLIN-III; Animals; Drosophila Proteins; RNA, Messenger; ADHESION MOLECULE; Databases, Protein; SPECIFICITY; Motor Neurons; POSTSYNAPTIC FILOPODIA; Gene Expression Profiling; Muscles; RECOGNITION; Membrane Proteins; FUNCTIONAL DISSECTION; Axons; Protein Structure, Tertiary; Insulin-Like Growth Factor Binding Proteins; DROSOPHILA; TRANSMEMBRANE PROTEIN; Larva; CELLBIO; Drosophila

In Drosophila embryos and larvae, a small number of identified motor neurons innervate body wall muscles in a highly stereotyped pattern. Although genetic screens have identified many proteins that are required for axon guidance and synaptogenesis in this system, little is known about the mechanisms by which muscle fibers are defined as targets for specific motor axons. To identify potential target labels, we screened 410 genes encoding cell-surface and secreted proteins, searching for those whose overexpression on all muscle fibers causes motor axons to make targeting errors. Thirty such genes were identified, and a number of these were members of a large gene family encoding proteins whose extracellular domains contain leucine-rich repeat (LRR) sequences, which are protein interaction modules. By manipulating gene expression in muscle 12, we showed that four LRR proteins participate in the selection of this muscle as the appropriate synaptic target for the RP5 motor neuron.