The Schizophrenia Susceptibility Gene dysbindin Controls Synaptic Homeostasis

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Abstract
Dysbindin Function in Synaptic Homeostasis: Homeostatic signaling systems are widely believed to stabilize neural function over prolonged periods of time. However, the molecular mechanisms of homeostatic signaling in the nervous system are largely unknown, and direct links between defective homeostatic signaling and disease-causing genes remain obscure. Dickman and Davis (p. 1127 ) performed a large-scale, electrophysiology-based genetic screen for mutations that specifically disrupt synaptic homeostasis. DTNBP1 is one of two genes that are most strongly and consistently associated with schizophrenia susceptibility in humans. The Drosophila homolog of DTNBP1 (dysbindin) was identified in the screen and was found to function during synapse development, baseline neurotransmission, and synaptic homeostasis. Dysbindin altered the calcium-dependence of vesicle release and was essential in the presynaptic neuron for both the induction and expression of synaptic homeostasis.

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