RNA Binding Proteins Accumulate at the Postsynaptic Density with Synaptic Activity
Open Access
- 11 January 2012
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 32 (2), 599-609
- https://doi.org/10.1523/jneurosci.2463-11.2012
Abstract
Neuronal activity elicits changes in synaptic composition that play an important role in experience-dependent plasticity (Choquet and Triller, 2003; Lisman and Raghavachari, 2006; Bourne and Harris, 2008; Holtmaat and Svoboda, 2009). We used a modified version of stable isotope labeling by amino acids in cell culture to identify activity-dependent modifications in the composition of postsynaptic densities (PSDs) isolated from rat primary neuronal cultures. We found that synaptic activity altered ∼2% of the PSD proteome, which included an increase in diverse RNA binding proteins (RNABPs). Indeed, 12 of the 37 identified proteins whose levels changed with synaptic activity were RNABPs and included the heterogeneous nuclear ribonucleoproteins (hnRNPs) G, A2/B1, M, and D. Knockdown of hnRNPs M and G using shRNAs resulted in altered numbers of dendritic spines, suggesting a crucial role for these proteins in spine density. Synaptic activity also resulted in a concomitant increase in dendritic and synaptic poly(A) mRNA. However, this increase was not affected by knockdown of hnRNPs M or G. Our results suggest that hnRNP proteins regulate dendritic spine density and may play a role in synaptodendritic mRNA metabolism.Keywords
This publication has 84 references indexed in Scilit:
- Study of Neurotrophin-3 Signaling in Primary Cultured Neurons using Multiplex Stable Isotope Labeling with Amino Acids in Cell CultureJournal of Proteome Research, 2011
- Cytoplasmic Intron Sequence-Retaining Transcripts Can Be Dendritically Targeted via ID Element RetrotransposonsNeuron, 2011
- Intron retention facilitates splice variant diversity in calcium-activated big potassium channel populationsProceedings of the National Academy of Sciences of the United States of America, 2010
- Experience-dependent structural synaptic plasticity in the mammalian brainNature Reviews Neuroscience, 2009
- Systematic and integrative analysis of large gene lists using DAVID bioinformatics resourcesNature Protocols, 2008
- MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantificationNature Biotechnology, 2008
- Sustained CPEB-Dependent Local Protein Synthesis Is Required to Stabilize Synaptic Growth for Persistence of Long-Term Facilitation in AplysiaNeuron, 2008
- Expression cloning in Xenopus identifies RNA‐binding proteins as regulators of embryogenesis and Rbmx as necessary for neural and muscle developmentDevelopmental Dynamics, 2008
- Stable Isotopic Labeling by Amino Acids in Cultured Primary NeuronsMolecular & Cellular Proteomics, 2008
- Cytoplasmic BK Ca channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neuronsProceedings of the National Academy of Sciences of the United States of America, 2008