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.

Title
The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration in Drosophila.
Author
Haberman, A.S., Williamson, W.R., Epstein, D., Wang, D., Rina, S., Meinertzhagen, I.A. and Hiesinger, P.R.
Publisher
Rockefeller University Press
Date
2012-01-23
Identifier
doi: 10.1083/jcb.201108088
Appeared in
J. Cell. Biol. 196(2): 261-276
Language
eng
Type
Text
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/).
NeuroCure