title: Local translation of RhoA regulates growth cone collapse.
abstract: Neuronal development requires highly coordinated regulation of the cytoskeleton within the developing axon. This dynamic regulation manifests itself in axonal branching, turning and pathfinding, presynaptic differentiation, and growth cone collapse and extension. Semaphorin 3A (Sema3A), a secreted guidance cue that primarily functions to repel axons from inappropriate targets, induces cytoskeletal rearrangements that result in growth cone collapse. These effects require intra-axonal messenger RNA translation. Here we show that transcripts for RhoA, a small guanosine triphosphatase (GTPase) that regulates the actin cytoskeleton, are localized to developing axons and growth cones, and this localization is mediated by an axonal targeting element located in the RhoA 3' untranslated region (UTR). Sema3A induces intra-axonal translation of RhoA mRNA, and this local translation of RhoA is necessary and sufficient for Sema3A-mediated growth cone collapse. These studies indicate that local RhoA translation regulates the neuronal cytoskeleton and identify a new mechanism for the regulation of RhoA signalling.
authors.affiliation: Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
authors.forename: Karen Y
authors.initials: KY
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hengst
authors.affiliation: Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
authors.forename: Llewellyn J
authors.initials: LJ
authors.lastname: Cox
authors.affiliation: Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
authors.forename: Evan Z
authors.initials: EZ
authors.lastname: Macosko
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jeromin
authors.affiliation: Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
authors.forename: Erica R
authors.initials: ER
authors.lastname: Urquhart
authors.affiliation: Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
authors.forename: Samie R
authors.initials: SR
authors.lastname: Jaffrey
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D017930:Genes, Reporter / Q000235:genetics; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis; D034443:RNA Transport; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D040121:Semaphorin-3A / Q000378:metabolism / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D034741:RNA, Small Interfering; D040121:Semaphorin-3A; D020742:rhoA GTP-Binding Protein