title: Time of day regulates subcellular trafficking, tripartite synaptic localization, and polyadenylation of the astrocytic Fabp7 mRNA.
abstract: The astrocyte brain fatty acid binding protein (Fabp7) has previously been shown to have a coordinated diurnal regulation of mRNA and protein throughout mouse brain, and an age-dependent decline in protein expression within synaptoneurosomal fractions. Mechanisms that control time-of-day changes in expression and trafficking Fabp7 to the perisynaptic process are not known. In this study, we confirmed an enrichment of Fabp7 mRNA and protein in the astrocytic perisynaptic compartment, and observed a diurnal change in the intracellular distribution of Fabp7 mRNA in molecular layers of hippocampus. Northern blotting revealed a coordinated time-of-day-dependent oscillation for the Fabp7 mRNA poly(A) tail throughout murine brain. Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) regulates subcellular trafficking and translation of synaptic plasticity-related mRNAs. Here we show that Fabp7 mRNA coimmunoprecipitated with CPEB1 from primary mouse astrocyte extracts, and its 3'UTR contains phylogenetically conserved cytoplasmic polyadenylation elements (CPEs) capable of regulating translation of reporter mRNAs during Xenopus oocyte maturation. Given that Fabp7 expression is confined to astrocytes and neural progenitors in adult mouse brain, the synchronized cycling pattern of Fabp7 mRNA is a novel discovery among known CPE-regulated transcripts. These results implicate circadian, sleep, and/or metabolic control of CPEB-mediated subcellular trafficking and localized translation of Fabp7 mRNA in the tripartite synapse of mammalian brain.
authors.affiliation: Center for Sleep and Circadian Neurobiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. gerstner@upenn.edu
authors.forename: Jason R
authors.initials: JR
authors.lastname: Gerstner
authors.forename: William M
authors.initials: WM
authors.lastname: Vanderheyden
authors.forename: Timothy
authors.initials: T
authors.lastname: LaVaute
authors.forename: Cara J
authors.initials: CJ
authors.lastname: Westmark
authors.forename: Labib
authors.initials: L
authors.lastname: Rouhana
authors.forename: Allan I
authors.initials: AI
authors.lastname: Pack
authors.forename: Marv
authors.initials: M
authors.lastname: Wickens
authors.forename: Charles F
authors.initials: CF
authors.lastname: Landry
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000502:physiology*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D026723:Polyadenylation / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism / Q000502:physiology; D013569:Synapses / Q000378:metabolism* / Q000502:physiology; D014981:Xenopus
chemical_list: C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger