Open AccessCell Type-Specific Effects of Mutant DISC1: A Proteomics Study
Author(s) -
Xin Meng,
Jantine A.C. Broek,
Yan Jouroukhin,
Jeannine Schoenfelder,
Sofya Abazyan,
Hanna Jaaro-Peled,
Akira Sawa,
Sabine Bahn,
Mikhail Pletnikov
Publication year - 2016
Publication title -
complex psychiatry
Language(s) - English
Resource type - Journals
eISSN - 2673-3005
pISSN - 2673-298X
DOI - 10.1159/000444587
Subject(s) - disc1 , mutant , biology , proteomics , schizophrenia (object oriented programming) , microbiology and biotechnology , neuroscience , genetics , gene , medicine , psychiatry
Despite the recent progress in psychiatric genetics, very few studies have focused on genetic risk factors in glial cells that, compared to neurons, can manifest different molecular pathologies underlying psychiatric disorders. In order to address this issue, we studied the effects of mutant disrupted in schizophrenia 1 (DISC1), a genetic risk factor for schizophrenia, in cultured primary neurons and astrocytes using an unbiased mass spectrometry-based proteomic approach. We found that selective expression of mutant DISC1 in neurons affects a wide variety of proteins predominantly involved in neuronal development (e.g., SOX1) and vesicular transport (Rab proteins), whereas selective expression of mutant DISC1 in astrocytes produces changes in the levels of mitochondrial (GDPM), nuclear (TMM43) and cell adhesion (ECM2) proteins. The present study demonstrates that DISC1 variants can perturb distinct molecular pathways in a cell type-specific fashion to contribute to psychiatric disorders through heterogenic effects in diverse brain cells.