Local translation of RhoA regulates growth cone collapse.
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.
Wu
Karen Y
KY
Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
Hengst
Ulrich
U
Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
Cox
Llewellyn J
LJ
Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
Macosko
Evan Z
EZ
Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
Jeromin
Andreas
A
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Urquhart
Erica R
ER
Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
Jaffrey
Samie R
SR
Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
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*
D020413:3' Untranslated Regions; D034741:RNA, Small Interfering; D040121:Semaphorin-3A; D020742:rhoA GTP-Binding Protein