title: Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons.
abstract: The Slit protein is a major midline repellent for central nervous system (CNS) axons. In vivo, Slit is proteolytically cleaved into N- and C-terminal fragments, but the biological significance of this is unknown. Analysis in the Drosophila ventral nerve cord of a slit allele (slit-UC) that cannot be cleaved revealed that midline repulsion is still present but longitudinal axon guidance is disrupted, particularly across segment boundaries. Double mutants for the Slit receptors Dscam1 and robo1 strongly resemble the slit-UC phenotype, suggesting they cooperate in longitudinal axon guidance, and through biochemical approaches, we found that Dscam1 and Robo1 form a complex dependent on Slit-N. In contrast, Robo1 binding alone shows a preference for full-length Slit, whereas Dscam1 only binds Slit-N. Using a variety of transgenes, we demonstrated that Dscam1 appears to modify the output of Robo/Slit complexes so that signaling is no longer repulsive. Our data suggest that the complex is promoting longitudinal axon growth across the segment boundary. The ability of Dscam1 to modify the output of other receptors in a ligand-dependent fashion may be a general principle for Dscam proteins.
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Maryam
authors.initials: M
authors.lastname: Alavi
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Minmin
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Gracie L Andrews
authors.identifier: 0000-0001-5611-9076
authors.initials: GL
authors.lastname: King
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Taylor
authors.initials: T
authors.lastname: Gillis
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Robert
authors.identifier: 0000-0001-9111-3710
authors.initials: R
authors.lastname: Propst
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Matthew
authors.identifier: 0000-0002-3473-1771
authors.initials: M
authors.lastname: Lamanuzzi
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Adam
authors.initials: A
authors.lastname: Bousum
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Miller
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Ryan
authors.identifier: 0000-0002-5002-038X
authors.initials: R
authors.lastname: Allen
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kidd
mesh_terms: D000483:Alleles; D000818:Animals; D001369:Axons / Q000378:metabolism*; D016367:Baculoviridae; D001665:Binding Sites; D019556:COS Cells; D015815:Cell Adhesion Molecules; D002460:Cell Line; D002522:Chlorocebus aethiops; D029721:Drosophila Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007313:Insecta; D008024:Ligands; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000075385:Netrins / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D010641:Phenotype; D000072417:Protein Domains; D011971:Receptors, Immunologic / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D019076:Transgenes; D000097905:Roundabout Proteins
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D008024:Ligands; D009419:Nerve Tissue Proteins; D000075385:Netrins; D019006:Neural Cell Adhesion Molecules; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D000097905:Roundabout Proteins; C491736:Dscam1 protein, Drosophila; C066819:sli protein, Drosophila