Selective reduction of a PDZ protein, SAP-97, in the prefrontal cortex of patients with chronic schizophrenia.
Many postsynaptic density proteins carrying postsynaptic density-95/discs large/zone occludens-1 (PDZ) domain(s) interact with glutamate receptors to control receptor dynamics and synaptic plasticity. Here we examined the expression of PDZ proteins, synapse-associated protein (SAP) 97, postsynaptic density (PSD)-95, chapsyn-110, GRIP1 and SAP102, in post-mortem brains of schizophrenic patients and control subjects, and evaluated their contribution to schizophrenic pathology. Among these PDZ proteins, SAP97 exhibited the most marked change: SAP97 protein levels were decreased to less than half that of the control levels specifically in the prefrontal cortex of schizophrenic patients. In parallel, its binding partner, GluR1, similarly decreased in the same brain region. The correlation between SAP97 and GluR1 levels in control subjects was, however, altered in schizophrenic patients. SAP102 levels were also significantly reduced in the hippocampus of schizophrenic patients, but this reduction was correlated with sample storage time and post-mortem interval. There were no changes in the levels of the other PDZ proteins in any of the regions examined. In addition, neuroleptic treatment failed to mimic the SAP97 change. These findings suggest that a phenotypic loss of SAP97 is associated with the postsynaptic impairment in prefrontal excitatory circuits of schizophrenic patients.
Toyooka
Kazuhiko
K
Molecular Neurobiology, Brain Research Institute, Niigata University, Japan.
Iritani
Shuji
S
Makifuchi
Takao
T
Shirakawa
Osamu
O
Kitamura
Noboru
N
Maeda
Kiyoshi
K
Nakamura
Ryosuke
R
Niizato
Kazuhiro
K
Watanabe
Masahiko
M
Kakita
Akiyoshi
A
Takahashi
Hitoshi
H
Someya
Toshiyuki
T
Nawa
Hiroyuki
H
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002908:Chronic Disease; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D051528:Guanylate Kinases; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D009479:Neuropeptides / Q000032:analysis / Q000096:biosynthesis; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D009703:Nucleoside-Phosphate Kinase / Q000032:analysis / Q000096:biosynthesis; D010084:Oxidation-Reduction; D017397:Prefrontal Cortex / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000032:analysis / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis
D048868:Adaptor Proteins, Signal Transducing; D014150:Antipsychotic Agents; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D006220:Haloperidol; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D009703:Nucleoside-Phosphate Kinase; D018091:Receptors, AMPA; D014157:Transcription Factors; C513314:DLG1 protein, human; C116869:DLG3 protein, human; C501119:Dlg1 protein, rat; C101195:Dlg3 protein, rat; C501449:Dlg4 protein, rat; C501451:Mpp2 protein, rat; C498001:NCOA2 protein, human; C498003:Ncoa2 protein, rat; C033652:postsynaptic density proteins