Proteomic analysis of membrane microdomain-associated proteins in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder reveals alterations in LAMP, STXBP1 and BASP1 protein expression.
AffiliationDepartment of Psychiatry, Royal College of Surgeons in Ireland, RCSI ERC, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland.
Cell Adhesion Molecules, Neuronal
Electrophoresis, Gel, Two-Dimensional
Electrophoresis, Polyacrylamide Gel
Nerve Tissue Proteins
Reproducibility of Results
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Tandem Mass Spectrometry
MetadataShow full item record
CitationProteomic analysis of membrane microdomain-associated proteins in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder reveals alterations in LAMP, STXBP1 and BASP1 protein expression. 2009, 14 (6):601-13 Mol. Psychiatry
AbstractThe dorsolateral prefrontal cortex (dlpfc) is strongly implicated in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BPD) and, within this region, abnormalities in glutamatergic neurotransmission and synaptic function have been described. Proteins associated with these functions are enriched in membrane microdomains (MM). In the current study, we used two complementary proteomic methods, two-dimensional difference gel electrophoresis and one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis followed by reverse phase-liquid chromatography-tandem mass spectrometry (RP-LC-MS/MS) (gel separation liquid chromatography-tandem mass spectrometry (GeLC-MS/MS)) to assess protein expression in MM in pooled samples of dlpfc from SCZ, BPD and control cases (n=10 per group) from the Stanley Foundation Brain series. We identified 16 proteins altered in one/both disorders using proteomic methods. We selected three proteins with roles in synaptic function (syntaxin-binding protein 1 (STXBP1), brain abundant membrane-attached signal protein 1 (BASP1) and limbic system-associated membrane protein (LAMP)) for validation by western blotting. This revealed significantly increased expression of these proteins in SCZ (STXBP1 (24% difference; P<0.001), BASP1 (40% difference; P<0.05) and LAMP (22% difference; P<0.01)) and BPD (STXBP1 (31% difference; P<0.001), BASP1 (23% difference; P<0.01) and LAMP (20% difference; P<0.01)) in the Stanley brain series (n=20 per group). Further validation in dlpfc from the Harvard brain subseries (n=10 per group) confirmed increased protein expression in SCZ of STXBP1 (18% difference; P<0.0001), BASP1 (14% difference; P<0.0001) but not LAMP (20% difference; P=0.14). No significant differences in STXBP1, BASP1 or LAMP protein expression in BPD dlpfc were observed. This study, through proteomic assessments of MM in dlpfc and validation in two brain series, strongly implicates LAMP, STXBP1 and BASP1 in SCZ and supports the view of a neuritic and synaptic dysfunction in the neuropathology of SCZ.
- Identification of protein biomarkers for schizophrenia and bipolar disorder in the postmortem prefrontal cortex using SELDI-TOF-MS ProteinChip profiling combined with MALDI-TOF-PSD-MS analysis.
- Authors: Novikova SI, He F, Cutrufello NJ, Lidow MS
- Issue date: 2006 Jul
- 2-D DIGE analysis implicates cytoskeletal abnormalities in psychiatric disease.
- Authors: English JA, Dicker P, Föcking M, Dunn MJ, Cotter DR
- Issue date: 2009 Jun
- Evidence for disease and antipsychotic medication effects in post-mortem brain from schizophrenia patients.
- Authors: Chan MK, Tsang TM, Harris LW, Guest PC, Holmes E, Bahn S
- Issue date: 2011 Dec
- Expression of RGS4 splice variants in dorsolateral prefrontal cortex of schizophrenic and bipolar disorder patients.
- Authors: Ding L, Hegde AN
- Issue date: 2009 Mar 15
- Lipid raft proteomics: analysis of in-solution digest of sodium dodecyl sulfate-solubilized lipid raft proteins by liquid chromatography-matrix-assisted laser desorption/ionization tandem mass spectrometry.
- Authors: Li N, Shaw AR, Zhang N, Mak A, Li L
- Issue date: 2004 Oct