title: The TRIM-NHL protein Brat promotes axon maintenance by repressing src64B expression.
abstract: The morphology and the connectivity of neuronal structures formed during early development must be actively maintained as the brain matures. Although impaired axon stability is associated with the progression of various neurological diseases, relatively little is known about the factors controlling this process. We identified Brain tumor (Brat), a conserved member of the TRIM-NHL family of proteins, as a new regulator of axon maintenance in Drosophila CNS. Brat function is dispensable for the initial growth of Mushroom Body axons, but is required for the stabilization of axon bundles. We found that Brat represses the translation of src64B, an upstream regulator of a conserved Rho-dependent pathway previously shown to promote axon retraction. Furthermore, brat phenotypes are phenocopied by src64B overexpression, and partially suppressed by reducing the levels of src64B or components of the Rho pathway, suggesting that brat promotes axon maintenance by downregulating the levels of Src64B. Finally, Brat regulates brain connectivity via its NHL domain, but independently of its previously described partners Nanos, Pumilio, and d4EHP. Thus, our results uncover a novel post-transcriptional regulatory mechanism that controls the maintenance of neuronal architecture by tuning the levels of a conserved rho-dependent signaling pathway.
authors.affiliation: Institute of Biology Valrose, University of Nice Sophia Antipolis, CNRS UMR7277, INSERM U1091, 06108 Nice Cedex 2, France and.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marchetti
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Ilka
authors.initials: I
authors.lastname: Reichardt
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Knoblich
authors.affiliation: Institute of Biology Valrose, University of Nice Sophia Antipolis, CNRS UMR7277, INSERM U1091, 06108 Nice Cedex 2, France and besse@unice.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Besse
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster; D009434:Neural Pathways / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D019061:src-Family Kinases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; C412783:brat protein, Drosophila; D011505:Protein-Tyrosine Kinases; C075699:Src64B protein, Drosophila; D019061:src-Family Kinases
keywords: Drosophila; axon maintenance; mushroom body; post-transcriptional