{"article_type":"original","file_date_updated":"2025-09-27T22:30:02Z","intvolume":" 45","volume":45,"ddc":["570"],"quality_controlled":"1","publisher":"Society for Neuroscience","citation":{"mla":"Stratigi, Aikaterini, et al. “Neuroendocrine Control of Synaptic Transmission by PHAC-1 in C. Elegans.” Journal of Neuroscience, vol. 45, no. 13, e1767232024, Society for Neuroscience, 2025, doi:10.1523/JNEUROSCI.1767-23.2024.","apa":"Stratigi, A., Soler-García, M., Krout, M., Shukla, S., de Bono, M., Richmond, J. E., & Laurent, P. (2025). Neuroendocrine control of synaptic transmission by PHAC-1 in C. elegans. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1767-23.2024","short":"A. Stratigi, M. Soler-García, M. Krout, S. Shukla, M. de Bono, J.E. Richmond, P. Laurent, Journal of Neuroscience 45 (2025).","ama":"Stratigi A, Soler-García M, Krout M, et al. Neuroendocrine control of synaptic transmission by PHAC-1 in C. elegans. Journal of Neuroscience. 2025;45(13). doi:10.1523/JNEUROSCI.1767-23.2024","ista":"Stratigi A, Soler-García M, Krout M, Shukla S, de Bono M, Richmond JE, Laurent P. 2025. Neuroendocrine control of synaptic transmission by PHAC-1 in C. elegans. Journal of Neuroscience. 45(13), e1767232024.","ieee":"A. Stratigi et al., “Neuroendocrine control of synaptic transmission by PHAC-1 in C. elegans,” Journal of Neuroscience, vol. 45, no. 13. Society for Neuroscience, 2025.","chicago":"Stratigi, Aikaterini, Miguel Soler-García, Mia Krout, Shikha Shukla, Mario de Bono, Janet E. Richmond, and Patrick Laurent. “Neuroendocrine Control of Synaptic Transmission by PHAC-1 in C. Elegans.” Journal of Neuroscience. Society for Neuroscience, 2025. https://doi.org/10.1523/JNEUROSCI.1767-23.2024."},"language":[{"iso":"eng"}],"author":[{"first_name":"Aikaterini","last_name":"Stratigi","full_name":"Stratigi, Aikaterini"},{"first_name":"Miguel","last_name":"Soler-García","full_name":"Soler-García, Miguel"},{"first_name":"Mia","last_name":"Krout","full_name":"Krout, Mia"},{"full_name":"Shukla, Shikha","last_name":"Shukla","first_name":"Shikha"},{"first_name":"Mario","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","full_name":"De Bono, Mario","last_name":"De Bono","orcid":"0000-0001-8347-0443"},{"first_name":"Janet E.","last_name":"Richmond","full_name":"Richmond, Janet E."},{"first_name":"Patrick","last_name":"Laurent","full_name":"Laurent, Patrick"}],"file":[{"creator":"dernst","date_created":"2025-04-07T11:57:19Z","checksum":"7befc0168f4cd5bd2b0fcff9e2a94784","content_type":"application/pdf","date_updated":"2025-09-27T22:30:02Z","file_name":"2025_JourNeuroscience_Stratigi.pdf","file_id":"19525","embargo":"2025-09-27","relation":"main_file","access_level":"open_access","file_size":3111735}],"_id":"19498","OA_place":"publisher","article_processing_charge":"No","department":[{"_id":"MaDe"}],"acknowledgement":"P.L. is a research associate of the Belgian National Fund for Scientific Research (FRS-FNRS). K.S., M.S.-G., S.S., and P.L. are supported by grants from the FRS-FNRS. This work was supported by an Advanced ERC Grant (269058 ACMO) to M.D.B. We thank the team of Alexander Gottschalk for the snn-1(S9A) strain. We thank the Imaging Facility of the Faculty of Medicine (LiMiF) of the Universite Libre de Bruxelles, supported by FRS-FNRS. This work made use of instruments in the Electron Microscopy Core of the University of Illinois Chicago Research Resources Center as well as the BioCryo facility of Northwestern University's NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern's MRSEC program (NSF DMR-2308691). Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).","oa_version":"Published Version","external_id":{"pmid":["39919830"],"isi":["001460952700001"]},"license":"https://creativecommons.org/licenses/by/4.0/","publication_status":"published","abstract":[{"text":"A dynamic interplay between fast synaptic signals and slower neuromodulatory signals controls the excitatory/inhibitory (E/I) balance within neuronal circuits. The mechanisms by which neuropeptide signaling is regulated to maintain E/I balance remain uncertain. We designed a genetic screen to isolate genes involved in the peptidergic maintenance of the E/I balance in the C. elegans motor circuit. This screen identified the C. elegans orthologs of the presynaptic phosphoprotein synapsin (snn-1) and the protein phosphatase 1 (PP1) regulatory subunit PHACTR1 (phac-1). We demonstrate that both phac-1 and snn-1 alter the motor behavior of C. elegans, and genetic interactions suggest that SNN-1 contributes to PP1-PHAC-1 holoenzyme signaling. De novo variants of human PHACTR1, associated with early-onset epilepsies [developmental and epileptic encephalopathy 70 (DEE70)], when expressed in C. elegans resulted in constitutive PP1-PHAC-1 holoenzyme activity. Unregulated PP1-PHAC-1 signaling alters the synapsin and actin cytoskeleton and increases neuropeptide release by cholinergic motor neurons, which secondarily affects the presynaptic vesicle cycle. Together, these results clarify the dominant mechanisms of action of the DEE70 alleles and suggest that altered neuropeptide release may alter E/I balance in DEE70.","lang":"eng"}],"day":"26","isi":1,"date_published":"2025-03-26T00:00:00Z","oa":1,"year":"2025","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"article_number":"e1767232024","scopus_import":"1","issue":"13","status":"public","OA_type":"hybrid","type":"journal_article","publication":"Journal of Neuroscience","date_created":"2025-04-06T22:01:32Z","publication_identifier":{"issn":["0270-6474"],"eissn":["1529-2401"]},"month":"03","title":"Neuroendocrine control of synaptic transmission by PHAC-1 in C. elegans","pmid":1,"doi":"10.1523/JNEUROSCI.1767-23.2024","has_accepted_license":"1","date_updated":"2025-09-30T11:29:28Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345"}