Format

Send to

Choose Destination
Biol Psychiatry. 2010 Feb 1;67(3):208-16. doi: 10.1016/j.biopsych.2009.07.029. Epub 2009 Sep 12.

Deficits in syntaxin 1 phosphorylation in schizophrenia prefrontal cortex.

Author information

1
Department of Neurology, The University of Texas, Southwestern Medical Center, Dallas, Texas, USA.

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.

PMID:
19748077
DOI:
10.1016/j.biopsych.2009.07.029
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center