Synapsin is required for dense core vesicle capture and cAMP-dependent neuropeptide release

  • Release of neuropeptides from dense core vesicles (DCVs) is essential for neuromodulation. Compared to the release of small neurotransmitters, much less is known about the mechanisms and proteins contributing to neuropeptide release. By optogenetics, behavioral analysis, electrophysiology, electron microscopy, and live imaging, we show that synapsin SNN-1 is required for cAMP-dependent neuropeptide release in Caenorhabditis elegans hermaphrodite cholinergic motor neurons. In synapsin mutants, behaviors induced by the photoactivated adenylyl cyclase bPAC, which we previously showed to depend on acetylcholine and neuropeptides (Steuer Costa et al., 2017), are altered like in animals with reduced cAMP. Synapsin mutants have slight alterations in synaptic vesicle (SV) distribution, however, a defect in SV mobilization was apparent after channelrhodopsin-based photostimulation. DCVs were largely affected in snn-1 mutants: DCVs were ∼30% reduced in synaptic terminals, and not released following bPAC stimulation. Imaging axonal DCV trafficking, also in genome-engineered mutants in the serine-9 protein kinase A phosphorylation site, showed that synapsin captures DCVs at synapses, making them available for release. SNN-1 co-localized with immobile, captured DCVs. In synapsin deletion mutants, DCVs were more mobile and less likely to be caught at release sites, and in non-phosphorylatable SNN-1B(S9A) mutants, DCVs traffic less and accumulate, likely by enhanced SNN-1 dependent tethering. Our work establishes synapsin as a key mediator of neuropeptide release.
Author:Szi-chieh Yu, Jana F. Liewald, Jiajie Shao, Wagner Steuer Costa, Alexander GottschalkORCiDGND
Parent Title (English):The journal of neuroscience : the official journal of the Society for Neuroscience
Publisher:Society for Neuroscience
Place of publication:Washington, DC
Document Type:Preprint
Date of Publication (online):2021/04/05
Date of first Publication:2021/04/05
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/04/08
Tag:Cellular neuroscience; Molecular Neuroscience
Page Number:39
This Early Release article has been peer-reviewed and accepted, but has not been through the composition and copyediting processes. The final version may differ slightly in style or formatting and will contain links to any extended data.
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoDeutsches Urheberrecht