title: The Control of semaphorin-1a-mediated reverse signaling by opposing pebble and RhoGAPp190 functions in drosophila.
abstract: Transmembrane semaphorins (Semas) serve evolutionarily conserved guidance roles, and some function as both ligands and receptors. However, the molecular mechanisms underlying the transduction of these signals to the cytoskeleton remain largely unknown. We have identified two direct regulators of Rho family small GTPases, pebble (a Rho guanine nucleotide exchange factor [GEF]) and RhoGAPp190 (a GTPase activating protein [GAP]), that show robust interactions with the cytoplasmic domain of the Drosophila Sema-1a protein. Neuronal pebble and RhoGAPp190 are required to control motor axon defasciculation at specific pathway choice points and also for target recognition during Drosophila neuromuscular development. Sema-1a-mediated motor axon defasciculation is promoted by pebble and inhibited by RhoGAPp190. Genetic analyses show that opposing pebble and RhoGAPp190 functions mediate Sema-1a reverse signaling through the regulation of Rho1 activity. Therefore, pebble and RhoGAPp190 transduce transmembrane semaphorin-mediated guidance cue information that regulates the establishment of neuronal connectivity during Drosophila development.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Sangyun
authors.initials: S
authors.lastname: Jeong
authors.forename: Katarina
authors.initials: K
authors.lastname: Juhaszova
authors.forename: Alex L
authors.initials: AL
authors.lastname: Kolodkin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D019521:Body Patterning / Q000235:genetics; D002461:Cell Line, Transformed; D048429:Cell Size; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D004625:Embryo, Nonmammalian; D053222:Fas Ligand Protein / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D005820:Genetic Testing; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D016296:Mutagenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology; D011485:Protein Binding / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014921:Wings, Animal / Q000196:embryology / Q000254:growth & development
chemical_list: D029721:Drosophila Proteins; D053222:Fas Ligand Protein; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; C121865:Pbl protein, Drosophila; D039961:Semaphorins; C085379:rho GTPase-activating protein