RIC-7 Promotes Neuropeptide Secretion

Yingsong Hao,Joshua M Kaplan,Derek Sieburth,Zhitao Hu,Andrew D Chisholm

doi:10.1371/journal.pgen.1002464

Yingsong Hao, Joshua M Kaplan + Show 3 more

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https://doi.org/10.1371/journal.pgen.1002464

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Abstract

Secretion of neurotransmitters and neuropeptides is mediated by exocytosis of distinct secretory organelles, synaptic vesicles (SVs) and dense core vesicles (DCVs) respectively. Relatively little is known about factors that differentially regulate SV and DCV secretion. Here we identify a novel protein RIC-7 that is required for neuropeptide secretion in Caenorhabditis elegans. The RIC-7 protein is expressed in all neurons and is localized to presynaptic terminals. Imaging, electrophysiology, and behavioral analysis of ric-7 mutants indicates that acetylcholine release occurs normally, while neuropeptide release is significantly decreased. These results suggest that RIC-7 promotes DCV–mediated secretion.

Highlights

Neuropeptides produce prolonged changes in circuit activity that are associated with changes in behavioral states; there is great interest in identifying molecules that are required for neuropeptide secretion
We show that a novel neuronal protein RIC-7 promotes neuropeptide secretion in C. elegans but has only subtle effects on neurotransmitter secretion
These results suggest that the machinery responsible for neuropeptide secretion evolved more recently than factors that are required for both neurotransmitter and neuropeptide secretion

Summary

Introduction

Neurotransmitters, such as acetylcholine (ACh), are secreted by exocytosis of small clear synaptic vesicles (SVs) whereas neuropeptide secretion is mediated by exocytosis of dense core vesicles (DCVs) [1,2]. SVs and DCVs both undergo physical docking to the plasma membrane, requiring Munc and syntaxin for docking in both cases [3,4,5,6,7]. SVs and DCVs must both undergo a priming reaction, which is mediated by priming factors (e.g. Munc and CAPS) [8,9]. Exocytosis of SVs and DCVs are both mediated by assembling complexes between vesicular and plasma membrane SNARE proteins [10,11]. Calcium-evoked fusion of SVs and DCVs are mediated by distinct calcium sensors, which are thought to be different synaptotagmin isoforms [12]

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