Deficits in Syntaxin 1 Phosphorylation in Schizophrenia Prefrontal Cortex

Max A. Castillo, Subroto Ghose, Carol A. Tamminga, Paula G. Ulery-Reynolds

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Background: Schizophrenia has been described as a disease of the synapse. On the basis of previous studies reporting reductions in the levels and activity of CK2 (also know as casein kinase 2 or II) in the brain of subjects with schizophrenia, we hypothesized that CK2-mediated phosphorylation of the presynaptic protein syntaxin 1 (Stx 1) is deficient in schizophrenia. This in turn could affect the binding of Stx 1 to its protein partners and result in abnormal neurotransmitter release and synaptic transmission. Methods: We analyzed post mortem prefrontal cortex samples from 15 schizophrenia cases and matched controls by quantitative immunoblotting. Results: In addition to replicating previous findings of reduced CK2 levels, we show that as predicted, the deficit in CK2 correlates with a deficit in phospho-Stx 1. In contrast, we find that these deficits are not present in depression cases. Further, we show that the reduced levels of CK2 and phospho-Stx 1 are not due to treatment with antipsychotic drugs (APDs). In fact, APDs seem to increase both CK2 and phospho-Stx 1, suggesting that their therapeutic action may be associated with the reversal of these deficits. Finally, we show that lower phospho-Stx 1 levels are associated with reduced binding of Stx 1 to SNAP-25 and MUNC18 and decreased SNARE complex formation. Conclusions: Our findings constitute the first report of altered phosphorylation of a key component for neurotransmitter release in humans and suggest that regulation of Stx 1 by CK2-mediated phosphorylation could play a role in the pathophysiology of schizophrenia.

Original languageEnglish (US)
Pages (from-to)208-216
Number of pages9
JournalBiological Psychiatry
Volume67
Issue number3
DOIs
StatePublished - Feb 1 2010

Keywords

  • Antipsychotic drugs
  • SNARE
  • Stx 1
  • phospho-specific antibody
  • post mortem
  • prefrontal cortex

ASJC Scopus subject areas

  • Biological Psychiatry

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