--- _id: '6109' abstract: - lang: eng text: 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. author: - first_name: Patrick full_name: Laurent, Patrick last_name: Laurent - first_name: QueeLim full_name: Ch’ng, QueeLim last_name: Ch’ng - first_name: Maëlle full_name: Jospin, Maëlle last_name: Jospin - first_name: Changchun full_name: Chen, Changchun last_name: Chen - first_name: Ramiro full_name: Lorenzo, Ramiro last_name: Lorenzo - first_name: Mario full_name: de Bono, Mario id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87 last_name: de Bono orcid: 0000-0001-8347-0443 citation: ama: Laurent P, Ch’ng Q, Jospin M, Chen C, Lorenzo R, de Bono M. Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron. Proceedings of the National Academy of Sciences. 2018;115(29):E6890-E6899. doi:10.1073/pnas.1714610115 apa: Laurent, P., Ch’ng, Q., Jospin, M., Chen, C., Lorenzo, R., & de Bono, M. (2018). Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1714610115 chicago: Laurent, Patrick, QueeLim Ch’ng, Maëlle Jospin, Changchun Chen, Ramiro Lorenzo, and Mario de Bono. “Genetic Dissection of Neuropeptide Cell Biology at High and Low Activity in a Defined Sensory Neuron.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2018. https://doi.org/10.1073/pnas.1714610115. ieee: P. Laurent, Q. Ch’ng, M. Jospin, C. Chen, R. Lorenzo, and M. de Bono, “Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron,” Proceedings of the National Academy of Sciences, vol. 115, no. 29. National Academy of Sciences, pp. E6890–E6899, 2018. ista: Laurent P, Ch’ng Q, Jospin M, Chen C, Lorenzo R, de Bono M. 2018. Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron. Proceedings of the National Academy of Sciences. 115(29), E6890–E6899. mla: Laurent, Patrick, et al. “Genetic Dissection of Neuropeptide Cell Biology at High and Low Activity in a Defined Sensory Neuron.” Proceedings of the National Academy of Sciences, vol. 115, no. 29, National Academy of Sciences, 2018, pp. E6890–99, doi:10.1073/pnas.1714610115. short: P. Laurent, Q. Ch’ng, M. Jospin, C. Chen, R. Lorenzo, M. de Bono, Proceedings of the National Academy of Sciences 115 (2018) E6890–E6899. date_created: 2019-03-19T12:41:33Z date_published: 2018-07-17T00:00:00Z date_updated: 2021-01-12T08:06:09Z day: '17' ddc: - '570' doi: 10.1073/pnas.1714610115 extern: '1' external_id: pmid: - '29959203' file: - access_level: open_access checksum: 5e81665377441cdd8d99ab952c534319 content_type: application/pdf creator: kschuh date_created: 2019-03-19T13:01:58Z date_updated: 2020-07-14T12:47:19Z file_id: '6110' file_name: 2018_PNAS_Laurent.pdf file_size: 1567765 relation: main_file file_date_updated: 2020-07-14T12:47:19Z has_accepted_license: '1' intvolume: ' 115' issue: '29' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: E6890-E6899 pmid: 1 publication: Proceedings of the National Academy of Sciences publication_identifier: issn: - 0027-8424 - 1091-6490 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' status: public title: Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 115 year: '2018' ...