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Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains
Journal article   Open access   Peer reviewed

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

Michael R Akins, Hanna E Berk-Rauch, Kenneth Y Kwan, Molly E Mitchell, Katherine A Shepard, Lulu I T Korsak, Emily E Stackpole, Jennifer L Warner-Schmidt, Nenad Sestan, Heather A Cameron, …
Human molecular genetics, v 26(1), pp 192-209
01 Jan 2017
DOI: https://doi.org/10.1093/hmg/ddw381
PMID: 28082376
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1093/hmg/ddw381View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Adult Animals Axons - metabolism Axons - pathology Brain - metabolism Brain - pathology Cytoplasmic Granules - metabolism Cytoplasmic Granules - pathology Fragile X Mental Retardation Protein - genetics Fragile X Mental Retardation Protein - metabolism Fragile X Syndrome - metabolism Fragile X Syndrome - pathology Hippocampus - metabolism Hippocampus - pathology Humans Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Neurogenesis - genetics Neurons - metabolism Neurons - pathology Rats Rats, Sprague-Dawley Ribosomes - metabolism Ribosomes - pathology RNA, Messenger - metabolism
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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Genetics & Heredity
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