In vivo quantitative proteomics of somatosensory cortical synapses shows which protein levels are modulated by sensory deprivation.
Postnatal bilateral whisker trimming was used as a model system to test how synaptic proteomes are altered in barrel cortex by sensory deprivation during synaptogenesis. Using quantitative mass spectrometry, we quantified more than 7,000 synaptic proteins and identified 89 significantly reduced and 161 significantly elevated proteins in sensory-deprived synapses, 22 of which were validated by immunoblotting. More than 95% of quantified proteins, including abundant synaptic proteins such as PSD-95 and gephyrin, exhibited no significant difference under high- and low-activity rearing conditions, suggesting no tissue-wide changes in excitatory or inhibitory synaptic density. In contrast, several proteins that promote mature spine morphology and synaptic strength, such as excitatory glutamate receptors and known accessory factors, were reduced significantly in deprived synapses. Immunohistochemistry revealed that the reduction in SynGAP1, a postsynaptic scaffolding protein, was restricted largely to layer I of barrel cortex in sensory-deprived rats. In addition, protein-degradation machinery such as proteasome subunits, E2 ligases, and E3 ligases, accumulated significantly in deprived synapses, suggesting targeted synaptic protein degradation under sensory deprivation. Importantly, this screen identified synaptic proteins whose levels were affected by sensory deprivation but whose synaptic roles have not yet been characterized in mammalian neurons. These data demonstrate the feasibility of defining synaptic proteomes under different sensory rearing conditions and could be applied to elucidate further molecular mechanisms of sensory development.
Proceedings of the National Academy of Sciences of the United States of America
February 19, 2013
Agency: NINDS NIH HHS, Id: 4R37NS027177-23
Agency: NIA NIH HHS, Id: F32 AG039127
Agency: NIA NIH HHS, Id: F32AG039127
Agency: NIA NIH HHS, Id: P01 AG031097
Agency: NIGMS NIH HHS, Id: P41 GM103533
Agency: NCRR NIH HHS, Id: P41 RR011823
Agency: NIMH NIH HHS, Id: R01 MH067880
Agency: Howard Hughes Medical Institute, Id:
Nerve Tissue Proteins
Tandem Mass Spectrometry
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