title: The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis.
abstract: The molecular mechanisms that achieve homeostatic stabilization of neural function remain largely unknown. To better understand how neural function is stabilized during development and throughout life, we used an electrophysiology-based forward genetic screen and assessed the function of more than 250 neuronally expressed genes for a role in the homeostatic modulation of synaptic transmission in Drosophila. This screen ruled out the involvement of numerous synaptic proteins and identified a critical function for dysbindin, a gene linked to schizophrenia in humans. We found that dysbindin is required presynaptically for the retrograde, homeostatic modulation of neurotransmission, and functions in a dose-dependent manner downstream or independently of calcium influx. Thus, dysbindin is essential for adaptive neural plasticity and may link altered homeostatic signaling with a complex neurological disease.
authors: Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
authors: Dion K
authors: DK
authors: Dickman
authors: Graeme W
authors: GW
authors: Davis
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D017344:Genes, Insect; D018698:Glutamic Acid / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D009154:Mutation; D009469:Neuromuscular Junction / Q000502:physiology; D009473:Neuronal Plasticity; D012559:Schizophrenia / Q000235:genetics; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism; D019076:Transgenes
chemical_list: D015220:Calcium Channels; D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D029721:Drosophila Proteins; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; C472405:cac protein, Drosophila; D018698:Glutamic Acid; D002118:Calcium