title: Drosophila neurexin IV interacts with Roundabout and is required for repulsive midline axon guidance.
abstract: Slit/Roundabout (Robo) signaling controls midline repulsive axon guidance. However, proteins that interact with Slit/Robo at the cell surface remain largely uncharacterized. Here, we report that the Drosophila transmembrane septate junction-specific protein Neurexin IV (Nrx IV) functions in midline repulsive axon guidance. Nrx IV is expressed in the neurons of the developing ventral nerve cord, and nrx IV mutants show crossing and circling of ipsilateral axons and fused commissures. Interestingly, the axon guidance defects observed in nrx IV mutants seem independent of its other binding partners, such as Contactin and Neuroglian and the midline glia protein Wrapper, which interacts in trans with Nrx IV. nrx IV mutants show diffuse Robo localization, and dose-dependent genetic interactions between nrx IV/robo and nrx IV/slit indicate that they function in a common pathway. In vivo biochemical studies reveal that Nrx IV associates with Robo, Slit, and Syndecan, and interactions between Robo and Slit, or Nrx IV and Slit, are affected in nrx IV and robo mutants, respectively. Coexpression of Nrx IV and Robo in mammalian cells confirms that these proteins retain the ability to interact in a heterologous system. Furthermore, we demonstrate that the extracellular region of Nrx IV is sufficient to rescue Robo localization and axon guidance phenotypes in nrx IV mutants. Together, our studies establish that Nrx IV is essential for proper Robo localization and identify Nrx IV as a novel interacting partner of the Slit/Robo signaling pathway.
authors.affiliation: Department of Cell and Molecular Physiology, University of North Carolina Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7545, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Banerjee
authors.forename: Kevin
authors.initials: K
authors.lastname: Blauth
authors.forename: Kimberly
authors.initials: K
authors.lastname: Peters
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Rogers
authors.forename: Alan S
authors.initials: AS
authors.lastname: Fanning
authors.forename: Manzoor A
authors.initials: MA
authors.lastname: Bhat
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D016466:CHO Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D000097905:Roundabout Proteins
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C491321:Nrx protein, Drosophila; C066819:sli protein, Drosophila
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