title: Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains.
abstract: Local mRNA translation in growing axons allows for rapid and precise regulation of protein expression in response to extrinsic stimuli. However, the role of local translation in mature CNS axons is unknown. Such a mechanism requires the presence of translational machinery and associated mRNAs in circuit-integrated brain axons. Here we use a combination of genetic, quantitative imaging and super-resolution microscopy approaches to show that mature axons in the mammalian brain contain ribosomes, the translational regulator FMRP and a subset of FMRP mRNA targets. This axonal translational machinery is associated with Fragile X granules (FXGs), which are restricted to axons in a stereotyped subset of brain circuits. FXGs and associated axonal translational machinery are present in hippocampus in humans as old as 57 years. This FXG-associated axonal translational machinery is present in adult rats, even when adult neurogenesis is blocked. In contrast, in mouse this machinery is only observed in juvenile hippocampal axons. This differential developmental expression was specific to the hippocampus, as both mice and rats exhibit FXGs in mature axons in the adult olfactory system. Experiments in Fmr1 null mice show that FMRP regulates axonal protein expression but is not required for axonal transport of ribosomes or its target mRNAs. Axonal translational machinery is thus a feature of adult CNS neurons. Regulation of this machinery by FMRP could support complex behaviours in humans throughout life.
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, USA.|Department of Neuroscience, Brown University, Providence, RI.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Akins
authors.affiliation: Department of Neuroscience, Brown University, Providence, RI.
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Berk-Rauch
authors.affiliation: Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Kenneth Y
authors.initials: KY
authors.lastname: Kwan
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, USA.
authors.forename: Molly E
authors.initials: ME
authors.lastname: Mitchell
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Shepard
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, USA.
authors.forename: Lulu I T
authors.initials: LI
authors.lastname: Korsak
authors.affiliation: Department of Neuroscience, Brown University, Providence, RI.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Stackpole
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Warner-Schmidt
authors.affiliation: Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Nenad
authors.initials: N
authors.lastname: Sestan
authors.affiliation: Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Cameron
authors.affiliation: Department of Neuroscience, Brown University, Providence, RI.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Fallon
mesh_terms: D000328:Adult; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000473:pathology; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000378:metabolism / Q000473:pathology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012270:Ribosomes / Q000378:metabolism / Q000473:pathology*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger