A protein essential for neurotransmitter release also helps neurons trash old proteins and protects against neurodegeneration, Haberman et al. reveal.
Neuronal synaptobrevin (n-Syb) is a SNARE protein that promotes membrane fusion, helping neurotransmitter-carrying vesicles to release their contents at the synaptic terminal. Another protein found on these vesicles, the v-ATPase pump that shuttles protons into the vesicle interior, appears to forestall neurodegeneration. Loss of V100, a key component of the ATPase, kills neurons in the Drosophila eye. The ATPase is part of a “sort-and-degrade” mechanism that dispatches vesicles that contain worn-out membrane proteins to the lysosome for destruction.
Haberman et al. found that fly eye neurons lacking n-Syb gradually died. Their synaptic terminals filled not with exocytic vesicles containing neurotransmitters but with endosomes carrying undegraded membrane cargo, suggesting that n-Syb also contributes to the sort-and-degrade mechanism.
n-Syb–deficient neurons teemed with vesicles that carried inert forms of cathepsins, enzymes that slice up proteins. Cathepsins are so destructive that they only switch on in the acidic interior of late endosomes, lysosomes, or autophagosomes. Haberman et al. think that n-Syb helps deliver cathepsin-containing endosomes from the Golgi and ER to the lysosome or late endosomes. Thus, by promoting the destruction of worn-out proteins, n-Syb prevents neurodegeneration. The researchers now want to investigate whether breakdown of this protective system can trigger neurodegenerative diseases.