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.
| Original language | English |
|---|---|
| Journal | Nature Neuroscience |
| Volume | 15 |
| Issue number | 3 |
| Pages (from-to) | 381-8, S1 |
| ISSN | 1097-6256 |
| DOIs | |
| Publication status | Published - Mar 2012 |
Keywords
- Age Factors
- Animals
- Carrier Proteins
- Cell Differentiation
- Cells, Cultured
- Cerebral Cortex
- Dendrites
- Electric Stimulation
- Electrophoretic Mobility Shift Assay
- Embryo, Mammalian
- Excitatory Postsynaptic Potentials
- Exons
- Gene Expression Regulation, Developmental
- Green Fluorescent Proteins
- Guanylate Kinase
- Hippocampus
- Homeodomain Proteins
- Membrane Proteins
- Mice
- Mice, Transgenic
- Neural Stem Cells
- Neuroblastoma
- Neurogenesis
- Neurons
- Patch-Clamp Techniques
- Polypyrimidine Tract-Binding Protein
- RNA Isoforms
- RNA Splicing
- RNA, Messenger
- RNA, Small Interfering
- Transcription Factors
- Transfection