title: Axonal protein synthesis provides a mechanism for localized regulation at an intermediate target.
abstract: As axons grow past intermediate targets, they change their responsiveness to guidance cues. Local upregulation of receptor expression is involved, but the mechanisms for this are not clear. Here protein synthesis is traced within individual axons by introducing RNAs encoding visualizable reporters. Individual severed axons and growth cones can translate proteins and also export them to the cell surface. As axons reach the spinal cord midline, EphA2 is among the receptors upregulated on at least some distal axon segments. Midline reporter upregulation is recapitulated by part of the EphA2 mRNA 3' untranslated region, which is highly conserved and includes known translational control sequences. These results show axons contain all the machinery for protein translation and cell surface expression, and they reveal a potentially general and flexible RNA-based mechanism for regulation localized within a subregion of the axon.
authors.affiliation: Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Perry A
authors.initials: PA
authors.lastname: Brittis
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lu
authors.forename: John G
authors.initials: JG
authors.lastname: Flanagan
mesh_terms: D020413:3' Untranslated Regions; D000469:Alkaline Phosphatase; D000818:Animals; D001369:Axons / Q000378:metabolism*; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D002642:Chick Embryo; D017124:Conserved Sequence; D019922:GAP-43 Protein / Q000096:biosynthesis; D058851:GPI-Linked Proteins; D015870:Gene Expression; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D020439:Growth Cones / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012313:RNA; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D036104:Receptor, EphA2; D012845:Sindbis Virus; D013116:Spinal Cord; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D019922:GAP-43 Protein; D058851:GPI-Linked Proteins; D007527:Isoenzymes; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D012313:RNA; D020794:Receptor Protein-Tyrosine Kinases; D036104:Receptor, EphA2; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental