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Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron

Research output: Contribution to journalArticlepeer-review

Patrick Laurent, Quee Lim Ch'ng, Maëlle Jospin, Changchun Chen, Ramiro Lorenzo, Mario De Bono

Original languageEnglish
Pages (from-to)E6890-E6899
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number29
Early online date29 Jun 2018
E-pub ahead of print29 Jun 2018
Published17 Jul 2018

King's Authors


Neuropeptides are ubiquitous modulators of behavior and physiology. They are packaged in specialized secretory organelles called dense core vesicles (DCVs) that are released upon neural stimulation. Unlike synaptic vesicles, which can be recycled and refilled close to release sites, DCVs must be replenished by de novo synthesis in the cell body. Here, we dissect DCV cell biology in vivo in a Caenorhabditis elegans sensory neuron whose tonic activity we can control using a natural stimulus. We express fluorescently tagged neuropeptides in the neuron and define parameters that describe their subcellular distribution. We measure these parameters at high and low neural activity in 187 mutants defective in proteins implicated in membrane traffic, neuroendocrine secretion, and neuronal or synaptic activity. Using unsupervised hierarchical clustering methods, we analyze these data and identify 62 groups of genes with similar mutant phenotypes. We explore the function of a subset of these groups. We recapitulate many previous findings, validating our paradigm. We uncover a large battery of proteins involved in recycling DCV membrane proteins, something hitherto poorly explored. We show that the unfolded protein response promotes DCV production, which may contribute to intertissue communication of stress. We also find evidence that different mechanisms of priming and exocytosis may operate at high and low neural activity. Our work provides a defined framework to study DCV biology at different neural activity levels.

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