title: Global quantitative analysis of phosphorylation underlying phencyclidine signaling and sensorimotor gating in the prefrontal cortex.
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.
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors: D B
authors: DB
authors: McClatchy
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors: J N
authors: JN
authors: Savas
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors: S
authors: S
authors: Martínez-Bartolomé
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors: S K
authors: SK
authors: Park
authors: Cellular Neurobiology Laboratory, Salk Institute, La Jolla, CA, USA.
authors: P
authors: P
authors: Maher
authors: Department of Psychiatry, UCSD, La Jolla, CA, USA.
authors: S B
authors: SB
authors: Powell
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors: J R
authors: JR
authors: Yates
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D004195:Disease Models, Animal; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D010622:Phencyclidine / Q000627:therapeutic use*; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000378:metabolism*; D065808:Prepulse Inhibition / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D012559:Schizophrenia / Q000378:metabolism; D055139:Sensory Gating / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D010622:Phencyclidine