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Haberman, A., Williamson, W.R., Epstein, D., Wang, D., Rina, S., Meinertzhagen, I.A., Hiesinger, P.R. (2012). The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration.  J. Cell Biol. 196(2): 261--276.
FlyBase ID
FBrf0217255
Publication Type
Research paper
Abstract

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.

PubMed ID
PubMed Central ID
PMC3265959 (PMC) (EuropePMC)
Related Publication(s)
Note

Autophagy, neuron-specific degradation and neurodegeneration.
Wang and Hiesinger, 2012, Autophagy 8(4): 711--713 [FBrf0219238]

Neuronal synaptobrevin promotes longevity in Drosophila photoreceptors.
Mejia and Haberman, 2012, Commun. Integr. Biol. 5(6): 620--622 [FBrf0221768]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Cell Biol.
    Title
    Journal of Cell Biology
    Publication Year
    1966-
    ISBN/ISSN
    0021-9525
    Data From Reference
    Genes (12)