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Featured ArticleArticles, Cellular/Molecular

Quantitative Proteomic and Genetic Analyses of the Schizophrenia Susceptibility Factor Dysbindin Identify Novel Roles of the Biogenesis of Lysosome-Related Organelles Complex 1

Avanti Gokhale, Jennifer Larimore, Erica Werner, Lomon So, Andres Moreno-De-Luca, Christa Lese-Martin, Vladimir V. Lupashin, Yoland Smith and Victor Faundez
Journal of Neuroscience 14 March 2012, 32 (11) 3697-3711; DOI: https://doi.org/10.1523/JNEUROSCI.5640-11.2012
Avanti Gokhale
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Jennifer Larimore
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Erica Werner
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Lomon So
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Andres Moreno-De-Luca
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Christa Lese-Martin
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Vladimir V. Lupashin
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Yoland Smith
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Victor Faundez
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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 (SILAC) quantitative proteomics 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.

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The Journal of Neuroscience: 32 (11)
Journal of Neuroscience
Vol. 32, Issue 11
14 Mar 2012
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Quantitative Proteomic and Genetic Analyses of the Schizophrenia Susceptibility Factor Dysbindin Identify Novel Roles of the Biogenesis of Lysosome-Related Organelles Complex 1
Avanti Gokhale, Jennifer Larimore, Erica Werner, Lomon So, Andres Moreno-De-Luca, Christa Lese-Martin, Vladimir V. Lupashin, Yoland Smith, Victor Faundez
Journal of Neuroscience 14 March 2012, 32 (11) 3697-3711; DOI: 10.1523/JNEUROSCI.5640-11.2012

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Quantitative Proteomic and Genetic Analyses of the Schizophrenia Susceptibility Factor Dysbindin Identify Novel Roles of the Biogenesis of Lysosome-Related Organelles Complex 1
Avanti Gokhale, Jennifer Larimore, Erica Werner, Lomon So, Andres Moreno-De-Luca, Christa Lese-Martin, Vladimir V. Lupashin, Yoland Smith, Victor Faundez
Journal of Neuroscience 14 March 2012, 32 (11) 3697-3711; DOI: 10.1523/JNEUROSCI.5640-11.2012
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