Soluble NSF attachment protein receptors (SNAREs) are the core proteins in membrane fusion. The neuron-specific synaptic v-SNARE n-syb (neuronal Synaptobrevin) plays a key role during synaptic vesicle exocytosis. In this paper, we report that loss of n-syb caused slow neurodegeneration independent of its role in neurotransmitter release in adult Drosophila melanogaster photoreceptor neurons. In addition to synaptic vesicles, n-Syb localized to endosomal vesicles. Loss of n-syb lead to endosomal accumulations, transmembrane protein degradation defects, and a secondary increase in autophagy. Our evidence suggests a primary defect of impaired delivery of vesicles that contain degradation proteins, including the acidification-activated Cathepsin proteases and the neuron-specific proton pump and V0 adenosine triphosphatase component V100. Overexpressing V100 partially rescued n-syb–dependent degeneration through an acidification-independent endosomal sorting mechanism. Collectively, these findings reveal a role for n-Syb in a neuron-specific sort-and-degrade mechanism that protects neurons from degeneration. Our findings further shed light on which intraneuronal compartments exhibit increased or decreased neurotoxicity.
Copyright © 2012 Haberman et al.
Published in final form at:
Haberman, A. S., Williamson, W. R., Epstein, D., Want, D., Rina, S., Meinertzhagen, I. A., and Hiesinger, P. R. (2012) The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysomal degradation and prevents neurodegeneration. The Journal of Cell Biology. 196(2), 261-76.
Digital USD Citation
Haberman, A. S., Williamson, W. R., Epstein, D., Wang, D., Rina, S., Meinerzhagen, I. A., and Hiesinger, P. R. (2012) The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosmal degradation and prevents neurodegenration. The Journal of Cell Biology. Biology Faculty Publications. Paper 5. http://digital.sandiego.edu/biology_facpub/5/