The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis

Science. 2009 Nov 20;326(5956):1127-30. doi: 10.1126/science.1179685.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Carrier Proteins / genetics
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / physiology*
  • Dysbindin
  • Dystrophin-Associated Proteins
  • Genes, Insect
  • Glutamic Acid / metabolism
  • Homeostasis
  • Humans
  • Mutation
  • Neuromuscular Junction / physiology
  • Neuronal Plasticity
  • Schizophrenia / genetics
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Synaptic Transmission*
  • Synaptic Vesicles / metabolism
  • Transgenes


  • Calcium Channels
  • Carrier Proteins
  • DTNBP1 protein, human
  • Drosophila Proteins
  • Dysbindin
  • Dystrophin-Associated Proteins
  • cac protein, Drosophila
  • Glutamic Acid
  • Calcium