title: Dysbindin-containing complexes and their proposed functions in brain: from zero to (too) many in a decade.
abstract: Dysbindin (also known as dysbindin-1 or dystrobrevin-binding protein 1) was identified 10 years ago as a ubiquitously expressed protein of unknown function. In the following years, the protein and its encoding gene, DTNBP1, have become the focus of intensive research owing to genetic and histopathological evidence suggesting a potential role in the pathogenesis of schizophrenia. In this review, we discuss published results demonstrating that dysbindin function is required for normal physiology of the mammalian central nervous system. In tissues other than brain and in non-neuronal cell types, the protein has been characterized as a stable component of a multi-subunit complex, named BLOC-1 (biogenesis of lysosome-related organelles complex-1), which has been implicated in intracellular protein trafficking and the biogenesis of specialized organelles of the endosomal-lysosomal system. In the brain, however, dysbindin has been proposed to associate into multiple complexes with alternative binding partners, and to play a surprisingly wide variety of functions including transcriptional regulation, neurite and dendritic spine formation, synaptic vesicle biogenesis and exocytosis, and trafficking of glutamate and dopamine receptors. This puzzling array of molecular and functional properties ascribed to the dysbindin protein from brain underscores the need of further research aimed at ascertaining its biological significance in health and disease.
authors.affiliation: Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California, Los Angeles, 90095, USA.
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Ghiani
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Dell'Angelica
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D000074765:Dysbindin; D016189:Dystrophin / Q000378:metabolism; D049029:Dystrophin-Associated Proteins; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D012559:Schizophrenia / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism
chemical_list: C104378:BLOC1S1 protein, human; D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; C120152:WASF2 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family