A Syntaxin1A protein mutation drives sleep reduction in Drosophila

Syntaxin1A is a key component in the regulation of the vesicle fusion nanomachine and, together with VAMP/synaptobrevin and SNAP-25, forms the core of the SNARE complex, that is the molecular nanomachine regulating neurotransmitter release. Syntaxin1A is localized on the cytosolic face of the presynaptic membrane and with Munc-18-1 is thought to be the starting point for the SNARE complex assembly. In flies, aspartic-to-arginine amino acid substitution at position 253 of the protein sequence reduces synaptic release by affecting the assembly of multiple SNARE complexes into a super-complex without interfering with the single complex formation per se. In this study, we analyzed sleep behavior in flies expressing this mutated isoform of Syntaxin1A pan-neuronally. According to the synaptic homeostasis hypothesis, the overall decrease of synaptic activity during the previous period of wakefulness should reduce the need for sleep. We observed a reduction in the total amount of sleep in flies expressing the mutated isoform compared to controls. Moreover, the sleep pattern of the Syntaxina1A mutant flies was more fragmented compared to controls. Video-tracking analysis of free walking flies in an open-field arena showed that these changes were not caused by higher locomotor activity during the daytime relative to controls. Our results suggest that the widespread effect of Syntaxin1A mutation on synapses may lead to a dampening of the information load among neurons and, consequently, impact the regulation of sleep at the cellular level.