title: PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2.
abstract: Postsynaptic density protein 95 (PSD-95) is essential for synaptic maturation and plasticity. Although its synaptic regulation has been widely studied, the control of PSD-95 cellular expression is not understood. We found that Psd-95 was controlled post-transcriptionally during neural development. Psd-95 was transcribed early in mouse embryonic brain, but most of its product transcripts were degraded. The polypyrimidine tract binding proteins PTBP1 and PTBP2 repressed Psd-95 (also known as Dlg4) exon 18 splicing, leading to premature translation termination and nonsense-mediated mRNA decay. The loss of first PTBP1 and then of PTBP2 during embryonic development allowed splicing of exon 18 and expression of PSD-95 late in neuronal maturation. Re-expression of PTBP1 or PTBP2 in differentiated neurons inhibited PSD-95 expression and impaired the development of glutamatergic synapses. Thus, expression of PSD-95 during early neural development is controlled at the RNA level by two PTB proteins whose sequential downregulation is necessary for synapse maturation.
authors.affiliation: Howard Hughes Medical Institute, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Sika
authors.initials: S
authors.lastname: Zheng
authors.forename: Erin E
authors.initials: EE
authors.lastname: Gray
authors.forename: Geetanjali
authors.initials: G
authors.lastname: Chawla
authors.forename: Bo Torben
authors.initials: BT
authors.lastname: Porse
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: O'Dell
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Black
mesh_terms: D000367:Age Factors; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003712:Dendrites / Q000235:genetics; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation; D024202:Electrophoretic Mobility Shift Assay; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D005091:Exons / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000502:physiology; D009447:Neuroblastoma / Q000473:pathology; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D059368:RNA Isoforms / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D038941:Polypyrimidine Tract-Binding Protein; D059368:RNA Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C501447:Dlg4 protein, mouse; C529977:Upf2 protein, mouse