Cytosolic protein interactions of the schizophrenia susceptibility gene dysbindin.
Using immunoprecipitation, mass spectrometry, and western blot analysis we investigated cytosolic protein interactions of the schizophrenia susceptibility gene dysbindin in mammalian cells. We identified novel interactions with members of the exocyst, dynactin and chaperonin containing T-complex protein complexes, and we confirmed interactions reported previously with all members of the biogenesis of lysosome-related organelles complex-1 and the adaptor-related protein complex 3. We report interactions between dysbindin and the exocyst and dynactin complex that confirm a link between two important schizophrenia susceptibility genes: dysbindin and disrupted-in-schizophrenia-1. To expand upon this network of interacting proteins we also investigated protein interactions for members of the exocyst and dynactin complexes in mammalian cells. Our results are consistent with the notion that impairment of aspects of the synaptic vesicle life cycle may be a pathogenic mechanism in schizophrenia.
Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
Carri-Lyn R
CL
Mead
Michael A
MA
Kuzyk
Annie
A
Moradian
Gary M
GM
Wilson
Robert A
RA
Holt
Gregg B
GB
Morin
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D016009:Chi-Square Distribution; D019295:Computational Biology; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005089:Exocytosis / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods
D002352:Carrier Proteins; C412476:DISC1 protein, human; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins