Differential proteome and phosphoproteome may impact cell signaling in the corpus callosum of schizophrenia patients

Author(s)

Saia-Cereda, Veronica M. ; Cassoli, Juliana S. ; Schmitt, Andrea ; Falkai, Peter ; Martins-de-Souza, Daniel

• Document type: Journal article
• Source: SCHIZOPHRENIA RESEARCH; v. 177, n. 1-3, p. 70-77, NOV 2016.
• Web of Science Citations: 8

Abstract

Schizophrenia is a multifactorial disease in both clinical and molecular terms. Thus, depicting the molecular aspects of the disease will contribute to the understanding of its biochemical mechanisms and consequently may lead to the development of new treatment strategies. The protein phosphorylation/dephosphorylation switch acts as the main mechanism for regulating cellular signaling. Moreover, approximately onethird of human proteins are phosphorylable. Thus, identifying proteins differentially phosphorylated in schizophrenia postmortem brains may improve our understanding of the molecular basis of brain function in this disease. Hence, we quantified the phosphoproteome of corpus callosum samples collected post mortem from schizophrenia patients and healthy controls. We used state-of-the-art, bottom-up shotgun mass spectrometry in a two-dimensional liquid chromatography-tandemmass spectrometry setup in the MS Emode with label-free quantification. We identified 60,634 peptides, belonging to 3283 proteins. Of these, 68 proteins were differentially phosphorylated, and 56 were differentially expressed. These proteins are mostly involved in signaling pathways, such as ephrin B and ciliary neurotrophic factor signaling. The data presented here are novel because this was the very first phosphoproteome analysis of schizophrenia brains. They support the important role of glial cells, especially astrocytes, in schizophrenia and help to further the understanding of the molecular aspects of this disease. Our findings indicate a need for further studies on cell signaling, which might shape the development of treatment strategies. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 14/10068-4 - Multi-User Equipment approved in grant 13/08711-3: mass spectrometer waters SYNAPT G2-Si HDMS + nanoACQUITY UPLC
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 14/14881-1 - Understanding the influence of glycolysis components in the function of oligodendrocytes: linking with findings in schizophrenia
• Grantee: Juliana Silva Cassoli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/08711-3 - Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Research Grants - Young Investigators Grants