Guidance Receptor Degradation Is Required for Neuronal Connectivity in the Drosophila Nervous System

University of Cambridge, United Kingdom
PLoS Biology (Impact Factor: 11.77). 12/2010; 8(12):e1000553. DOI: 10.1371/journal.pbio.1000553
Source: PubMed

ABSTRACT Author Summary
Brain wiring is determined by genetic and environmental factors, nature and nurture. The Drosophila brain is a model for the genetic basis of brain wiring. The fly visual system in particular is thought to be “hard-wired,” i.e., encoded solely by a genetic program. Some key genes encode the guidance receptors that serve as “wiring” and synaptic connectivity signals. However, it is poorly understood how guidance receptors are spatiotemporally regulated to serve as meaningful synapse formation signals. Indeed, many genes required for brain wiring do not encode the guidance receptors themselves, but rather encode parts of the cell biological machinery that governs their spatiotemporal signaling dynamics. For example, the vesicular ATPase is an intracellular sorting and acidification complex involved in regulating guidance receptor turnover and signaling. The protein V100 is a member of this v-ATPase complex, and in this study we show that mutations in the v100 gene cause brain wiring defects specifically in the adult brain. We further describe a V100-dependent intracellular “sort-and-degrade” mechanism that is required in neurons, and find that when this mechanism is perturbed, it leads to progressive build-up of and aberrant signaling by guidance receptors. These data suggest that a v100-dependent neuronal degradation mechanism provides a cell biological basis for guidance receptor turnover and spatiotemporally controlled dynamics during neural circuit formation.

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