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Global quantitative analysis of phosphorylation underlying phencyclidine signaling and sensorimotor gating in the prefrontal cortex

Molecular Psychiatry volume 21, pages 205–215 (2016)Cite this article

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Abstract

Prepulse inhibition (PPI) is an example of sensorimotor gating and deficits in PPI have been demonstrated in schizophrenia patients. Phencyclidine (PCP) suppression of PPI in animals has been studied to elucidate the pathological elements of schizophrenia. However, the molecular mechanisms underlying PCP treatment or PPI in the brain are still poorly understood. In this study, quantitative phosphoproteomic analysis was performed on the prefrontal cortex from rats that were subjected to PPI after being systemically injected with PCP or saline. PCP downregulated phosphorylation events were significantly enriched in proteins associated with long-term potentiation (LTP). Importantly, this data set identifies functionally novel phosphorylation sites on known LTP-associated signaling molecules. In addition, mutagenesis of a significantly altered phosphorylation site on xCT (SLC7A11), the light chain of system xc-, the cystine/glutamate antiporter, suggests that PCP also regulates the activity of this protein. Finally, new insights were also derived on PPI signaling independent of PCP treatment. This is the first quantitative phosphorylation proteomic analysis providing new molecular insights into sensorimotor gating.

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Acknowledgements

Funding has been provided by National Institutes of Health grants P41 GM103533, R01 MH067880 and R01 DA002925.

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Authors and Affiliations

  1. Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA,

    D B McClatchy, J N Savas, S Martínez-Bartolomé, S K Park & J R Yates III

  2. Cellular Neurobiology Laboratory, Salk Institute, La Jolla, CA, USA,

    P Maher

  3. Department of Psychiatry, UCSD, La Jolla, CA, USA,

    S B Powell

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  1. D B McClatchy
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  2. J N Savas
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  3. S Martínez-Bartolomé
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  7. J R Yates III
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Correspondence to J R Yates III.

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McClatchy, D., Savas, J., Martínez-Bartolomé, S. et al. Global quantitative analysis of phosphorylation underlying phencyclidine signaling and sensorimotor gating in the prefrontal cortex. Mol Psychiatry 21, 205–215 (2016). https://doi.org/10.1038/mp.2015.41

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  • DOI: https://doi.org/10.1038/mp.2015.41

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