The synaptic vesicle SNARE neuronal synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration

Adam Haberman, W. Ryan Williamson, Daniel Epstein, Dong Wang, Srisha Rina, Ian A. Meinertzhagen, P. Robin Hiesinger

Research output: Contribution to journalArticle

23 Scopus citations

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 sortand- degrade mechanism that protects neurons from degeneration. Our findings further shed light on which intraneuronal compartments exhibit increased or decreased neurotoxicity.

Original languageEnglish (US)
Pages (from-to)261-276
Number of pages16
JournalJournal of Cell Biology
Volume196
Issue number2
DOIs
StatePublished - Jan 2012

ASJC Scopus subject areas

  • Cell Biology

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