The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration in Drosophila.

jcb_cover2012big
jcb_cover2012big

Haberman, A.S., Williamson, W.R., Epstein, D., Wang, D., Rina, S., Meinertzhagen, I.A. and Hiesinger, P.R.— 2012

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.

TitleThe synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration in Drosophila.
AuthorHaberman, A.S., Williamson, W.R., Epstein, D., Wang, D., Rina, S., Meinertzhagen, I.A. and Hiesinger, P.R.
PublisherRockefeller University Press
Date20120123
Identifierdoi: 10.1083/jcb.201108088
Source(s)
Appeared InJ. Cell. Biol. 196(2): 261-276
Languageeng
TypeText
Rights© 2012 Haberman et al. Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).