title: Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay.
abstract: Growth cones enable axons to navigate toward their targets by responding to extracellular signaling molecules. Growth-cone responses are mediated in part by the local translation of axonal messenger RNAs (mRNAs). However, the mechanisms that regulate local translation are poorly understood. Here we show that Robo3.2, a receptor for the Slit family of guidance cues, is synthesized locally within axons of commissural neurons. Robo3.2 translation is induced by floor-plate-derived signals as axons cross the spinal cord midline. Robo3.2 is also a predicted target of the nonsense-mediated mRNA decay (NMD) pathway. We find that NMD regulates Robo3.2 synthesis by inducing the degradation of Robo3.2 transcripts in axons that encounter the floor plate. Commissural neurons deficient in NMD proteins exhibit aberrant axonal trajectories after crossing the midline, consistent with misregulation of Robo3.2 expression. These data show that local translation is regulated by mRNA stability and that NMD acts locally to influence axonal pathfinding.
authors.affiliation: Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10065, USA.
authors.forename: Dilek
authors.initials: D
authors.lastname: Colak
authors.forename: Sheng-Jian
authors.initials: SJ
authors.lastname: Ji
authors.forename: Bo T
authors.initials: BT
authors.lastname: Porse
authors.forename: Samie R
authors.initials: SR
authors.lastname: Jaffrey
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D059365:Nonsense Mediated mRNA Decay; D014176:Protein Biosynthesis; D059368:RNA Isoforms / Q000378:metabolism; D020871:RNA Stability; D011956:Receptors, Cell Surface; D013116:Spinal Cord / Q000196:embryology* / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D059368:RNA Isoforms; D011956:Receptors, Cell Surface; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins