About this item:

502 Views | 0 Downloads

Author Notes:

Address correspondence to: Victor Faundez, Department of Cell Biology, Emory University School of Medicine, 615 Michael Street, Room 446, Atlanta, GA 30322, Telephone: 404-727-3900, Fax: 404-727-6256, vfaunde@emory.edu

Subjects:

Research Funding:

This work was supported by grants from the National Institutes of Health to V.F. (NS42599, GM077569) and V.L. (GM083144). AG and JL were supported by National Institutes of Health FIRST program Fellowship K12 GM000680. Supported in part by the Neuronal Imaging Core of the Emory Neuroscience NINDS Core Facilities Grant P30NS055077 and by the Flow Cytometry Core Facility of the Emory University School of Medicine.

Quantitative Proteomic and Genetic Analyses of the Schizophrenia Susceptibility Factor Dysbindin Identify Novel Roles of the BLOC-1 Complex

Tools:

Journal Title:

Journal of Neuroscience Nursing

Volume:

Volume 32, Number 11

Publisher:

, Pages 3697-3711

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The Biogenesis of Lysosome-Related Organelles Complex 1 (BLOC-1) is a protein complex containing the schizophrenia susceptibility factor dysbindin, which is encoded by the gene DTNBP1. However, mechanisms engaged by dysbindin defining schizophrenia susceptibility pathways have not been quantitatively elucidated. Here, we discovered prevalent and novel cellular roles of the BLOC-1 complex in neuronal cells by performing large-scale Stable Isotopic Labeling of Cells in Culture quantitative proteomics (SILAC) combined with genetic analyses in dysbindin-null mice (Mus musculus) and the genome of schizophrenia patients. We identified 24 proteins that associate with the BLOC-1 complex many of which were altered in content/distribution in cells or tissues deficient in BLOC-1. New findings include BLOC-1 interactions with the COG complex, a Golgi apparatus tether, and antioxidant enzymes peroxiredoxins 1-2. Importantly, loci encoding eight of the 24 proteins are affected by genomic copy number variation in schizophrenia patients. Thus, our quantitative proteomic studies expand the functional repertoire of the BLOC-1 complex and provide insight into putative molecular pathways of schizophrenia susceptibility.

Copyright information:

© 2012 the authors

Export to EndNote