---
OA_place: publisher
OA_type: hybrid
_id: '19498'
abstract:
- lang: eng
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.
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).
article_number: e1767232024
article_processing_charge: No
article_type: original
author:
- first_name: Aikaterini
full_name: Stratigi, Aikaterini
last_name: Stratigi
- first_name: Miguel
full_name: Soler-García, Miguel
last_name: Soler-García
- first_name: Mia
full_name: Krout, Mia
last_name: Krout
- first_name: Shikha
full_name: Shukla, Shikha
last_name: Shukla
- first_name: Mario
full_name: De Bono, Mario
id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87
last_name: De Bono
orcid: 0000-0001-8347-0443
- first_name: Janet E.
full_name: Richmond, Janet E.
last_name: Richmond
- first_name: Patrick
full_name: Laurent, Patrick
last_name: Laurent
citation:
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
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
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.
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.
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.
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.
short: A. Stratigi, M. Soler-García, M. Krout, S. Shukla, M. de Bono, J.E. Richmond,
P. Laurent, Journal of Neuroscience 45 (2025).
date_created: 2025-04-06T22:01:32Z
date_published: 2025-03-26T00:00:00Z
date_updated: 2025-09-30T11:29:28Z
day: '26'
ddc:
- '570'
department:
- _id: MaDe
doi: 10.1523/JNEUROSCI.1767-23.2024
external_id:
isi:
- '001460952700001'
pmid:
- '39919830'
file:
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checksum: 7befc0168f4cd5bd2b0fcff9e2a94784
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creator: dernst
date_created: 2025-04-07T11:57:19Z
date_updated: 2025-09-27T22:30:02Z
embargo: 2025-09-27
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file_date_updated: 2025-09-27T22:30:02Z
has_accepted_license: '1'
intvolume: ' 45'
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language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: Journal of Neuroscience
publication_identifier:
eissn:
- 1529-2401
issn:
- 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: Neuroendocrine control of synaptic transmission by PHAC-1 in C. elegans
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 45
year: '2025'
...