The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth
| Autor: | Marta Starcevic, Esteban C. Dell'Angelica, Ramin Nazarian, J. de Vellis, Jemily S. Malvar, Chiara Sabatti, Cristina A. Ghiani, Imilce A. Rodriguez-Fernandez, L N Chan, Veronica T. Cheli |
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| Rok vydání: | 2009 |
| Předmět: |
Vesicle-Associated Membrane Protein 2
DTNBP1 biological plausibility Hippocampus Mice 0302 clinical medicine Syntaxin susceptibility gene neurite extension Cells Cultured Mice Knockout Neurons 0303 health sciences synaptosomal-associated protein Qa-SNARE Proteins Dysbindin Gene Expression Regulation Developmental Recombinant Proteins Transport protein Cell biology Psychiatry and Mental health Protein Transport Synaptosomal-Associated Protein 25 SNARE Proteins syntaxin Protein Binding Neurite Nerve Tissue Proteins Biology Synaptic vesicle Article 03 medical and health sciences Cellular and Molecular Neuroscience Neurites Animals Molecular Biology 030304 developmental biology Analysis of Variance pallidin Embryo Mammalian Mice Inbred C57BL schizophrenia Animals Newborn Dystrophin-Associated Proteins Mutation Cattle Organelle biogenesis Carrier Proteins Neuroscience 030217 neurology & neurosurgery primary cell culture |
| Zdroj: | Molecular psychiatry |
| ISSN: | 1476-5578 |
| Popis: | Previous studies have implicated DTNBP1 as a schizophrenia susceptibility gene and its encoded protein, dysbindin, as a potential regulator of synaptic vesicle physiology. In this study, we found that endogenous levels of the dysbindin protein in the mouse brain are developmentally regulated, with higher levels observed during embryonic and early postnatal ages than in young adulthood. We obtained biochemical evidence indicating that the bulk of dysbindin from brain exists as a stable component of biogenesis of lysosome-related organelles complex-1 (BLOC-1), a multi-subunit protein complex involved in intracellular membrane trafficking and organelle biogenesis. Selective biochemical interaction between brain BLOC-1 and a few members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) superfamily of proteins that control membrane fusion, including SNAP-25 and syntaxin 13, was demonstrated. Furthermore, primary hippocampal neurons deficient in BLOC-1 displayed neurite outgrowth defects. Taken together, these observations suggest a novel role for the dysbindin-containing complex, BLOC-1, in neurodevelopment, and provide a framework for considering potential effects of allelic variants in DTNBP1--or in other genes encoding BLOC-1 subunits--in the context of the developmental model of schizophrenia pathogenesis. |
| Databáze: | OpenAIRE |
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