• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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.

Pubmed ID: 23382246

Authors

  • Butko MT
  • Savas JN
  • Friedman B
  • Delahunty C
  • Ebner F
  • Yates JR
  • Tsien RY

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

February 19, 2013

Associated Grants

  • 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:

Mesh Terms

  • Animals
  • Immunohistochemistry
  • Mice
  • Microscopy, Electron
  • Nerve Tissue Proteins
  • Proteomics
  • Sensory Deprivation
  • Synapses
  • Tandem Mass Spectrometry