title: Requirement of Neuronal Ribosome Synthesis for Growth and Maintenance of the Dendritic Tree.
abstract: The nucleolus serves as a principal site of ribosome biogenesis but is also implicated in various non-ribosomal functions, including negative regulation of the pro-apoptotic transcription factor p53. Although disruption of the nucleolus may trigger the p53-dependent neuronal death, neurotoxic consequences of a selective impairment of ribosome production are unclear. Here, we report that in rat forebrain neuronal maturation is associated with a remarkable expansion of ribosomes despite postnatal down-regulation of ribosomal biogenesis. In cultured rat hippocampal neurons, inhibition of the latter process by knockdowns of ribosomal proteins S6, S14, or L4 reduced ribosome content without disrupting nucleolar integrity, cell survival, and signaling responses to the neurotrophin brain-derived neurotrophic factor. Moreover, reduced general protein synthesis and/or formation of RNA stress granules suggested diminished ribosome recruitment to at least some mRNAs. Such a translational insufficiency was accompanied by impairment of brain-derived neurotrophic factor-mediated dendritic growth. Finally, RNA stress granules and smaller dendritic trees were also observed when ribosomal proteins were depleted from neurons with established dendrites. Thus, a robust ribosomal apparatus is required to carry out protein synthesis that supports dendritic growth and maintenance. Consequently, deficits of ribosomal biogenesis may disturb neurodevelopment by reducing neuronal connectivity. Finally, as stress granule formation and dendritic loss occur early in neurodegenerative diseases, disrupted homeostasis of ribosomes may initiate and/or amplify neurodegeneration-associated disconnection of neuronal circuitries.
authors.affiliation: From the Kentucky Spinal Cord Injury Research Center and the Department of Neurological Surgery and.
authors.forename: Lukasz P
authors.initials: LP
authors.lastname: Slomnicki
authors.affiliation: From the Kentucky Spinal Cord Injury Research Center and the Department of Neurological Surgery and.
authors.forename: Maciej
authors.initials: M
authors.lastname: Pietrzak
authors.affiliation: From the Kentucky Spinal Cord Injury Research Center and the Department of Neurological Surgery and.
authors.forename: Aruna
authors.initials: A
authors.lastname: Vashishta
authors.affiliation: From the Kentucky Spinal Cord Injury Research Center and the Department of Neurological Surgery and.
authors.forename: James
authors.initials: J
authors.lastname: Jones
authors.affiliation: From the Kentucky Spinal Cord Injury Research Center and the Department of Neurological Surgery and.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lynch
authors.affiliation: From the Kentucky Spinal Cord Injury Research Center and the Department of Neurological Surgery and.
authors.forename: Shane
authors.initials: S
authors.lastname: Elliot
authors.affiliation: From the Kentucky Spinal Cord Injury Research Center and the Department of Neurological Surgery and.
authors.forename: Eric
authors.initials: E
authors.lastname: Poulos
authors.affiliation: From the Kentucky Spinal Cord Injury Research Center and the Department of Neurological Surgery and.
authors.forename: David
authors.initials: D
authors.lastname: Malicote
authors.affiliation: From the Kentucky Spinal Cord Injury Research Center and the Department of Neurological Surgery and.
authors.forename: Bridgit E
authors.initials: BE
authors.lastname: Morris
authors.affiliation: From the Kentucky Spinal Cord Injury Research Center and the Department of Neurological Surgery and.
authors.forename: Justin
authors.initials: J
authors.lastname: Hallgren
authors.affiliation: From the Kentucky Spinal Cord Injury Research Center and the Department of Neurological Surgery and; Departments of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky 40292. Electronic address: michal.hetman@louisville.edu.
authors.forename: Michal
authors.initials: M
authors.lastname: Hetman
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure*; D015536:Down-Regulation; D005260:Female; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D016548:Prosencephalon / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D014176:Protein Biosynthesis; D017207:Rats, Sprague-Dawley; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012269:Ribosomal Proteins
keywords: neurite outgrowth; neurodegeneration; neurodevelopment; neurotrophin; nucleolus; ribosome