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Published on: July 31, 2013
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Activity-Induced Cortical Glutamatergic Neuron Nascent Proteins
Lucio M Schiapparelli1, Yi Xie1,2, Pranav Sharma1,3
1Neuroscience Department and Dorris Neuroscience Center, Scripps Research Institute, La Jolla, California 92037.
Summary
This study quantifies activity-induced changes in newly synthesized proteins (NSPs) in specific brain cells. Researchers identified ~300 NSPs that change after seizure, revealing new insights into neuronal plasticity.
Area of Science:
- Neuroscience
- Proteomics
- Molecular Biology
Background:
- Neuronal activity drives plasticity and metabolic changes through signaling cascades.
- Understanding cell-specific protein synthesis dynamics in vivo is challenging due to heterogeneity and low protein abundance.
Purpose of the Study:
- To quantitatively analyze cell-specific activity-induced dynamics of newly synthesized proteins (NSPs) in vivo.
- To identify NSPs involved in neuronal plasticity and homeostatic mechanisms following seizure.
Main Methods:
- Utilized targeted expression of mutant methionine tRNA synthetase (MetRS) in genetically defined cortical glutamatergic neurons.
- Employed azidonorleucine labeling of NSPs followed by biotinylation and mass spectrometry after pharmacologically induced seizure in mice.
- Quantified activity-induced changes in NSPs from purified, biotinylated peptides.
Main Results:
- Identified significant changes in approximately 300 newly synthesized proteins (NSPs) in response to seizure.
- Found differential synthesis of proteins involved in synaptic plasticity (e.g., SynGAP1, Pak3) and chromatin remodeling (e.g., Rad21, Smarca2).
- Observed induction of proteins related to proteostasis, ion control, and cytoskeleton remodeling, while some proteins like NCAM showed decreased synthesis.
Conclusions:
- Developed a method to quantify activity-induced nascent proteome changes in genetically defined neurons.
- Discovered diverse roles for newly synthesized proteins in synaptic plasticity, chromatin remodeling, and homeostatic regulation.
- Generated hypotheses regarding the functional roles of identified NSPs in neuronal responses to activity.
