---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '22733'
abstract:
- lang: eng
  text: Sleep need is associated with both circuit dynamics and widespread synaptic
    plasticity, yet the specific synaptic changes underlying sleep homeostasis remain
    incompletely understood. In Drosophila, sleep loss has been shown to trigger plasticity
    of the presynaptic active zone, marked by increasing levels of the ELKS-family
    scaffold protein Bruchpilot (BRP). By titrating brp gene copy number, we previously
    established a presynapse-specific, dosage-dependent paradigm that modulates sleep
    pressure. Here, to elucidate the molecular landscape of this plasticity, we performed
    synapse-enriched integrated-omics. Proteomic and bioinformatic analyses revealed
    changes in immune and stress response pathways and local translation control.
    Strikingly, phospho-proteomic analysis uncovered a global shift toward hypophosphorylation,
    particularly in presynaptic proteins, indicating a reprogramming of the phosphorylation–dephosphorylation
    balance. This presynaptic hypophosphorylation is likely contributed by reduced
    activity of Protein Kinase A (PKA) and enhanced substrate affinity of Protein
    Phosphatase 1 (PP1) mediated by its regulatory subunit Spinophilin (Spn). Manipulating
    either PKA or PP1 activity was sufficient to suppress BRP-modulated sleep phenotypes.
    We propose that presynaptic hypophosphorylation constitutes a molecular signature
    of local synaptic remodeling that adaptively tunes sleep need via reversible posttranslational
    modification, a mechanism likely conserved across species.
article_number: e2524065123
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Chengji
  full_name: Piao, Chengji
  last_name: Piao
- first_name: Ewelina
  full_name: Dutkiewicz, Ewelina
  id: 0601cc46-c082-11ec-9b07-bb29641d1de9
  last_name: Dutkiewicz
- first_name: Laxmikanth
  full_name: Kollipara, Laxmikanth
  last_name: Kollipara
- first_name: Albert
  full_name: Sickmann, Albert
  last_name: Sickmann
- first_name: Sheng
  full_name: Huang, Sheng
  last_name: Huang
- first_name: Stephan J.
  full_name: Sigrist, Stephan J.
  last_name: Sigrist
citation:
  ama: Piao C, Dutkiewicz E, Kollipara L, Sickmann A, Huang S, Sigrist SJ. Active
    zone plasticity couples sleep need to presynaptic hypophosphorylation. <i>Proceedings
    of the National Academy of Sciences</i>. 2026;123(24). doi:<a href="https://doi.org/10.1073/pnas.2524065123">10.1073/pnas.2524065123</a>
  apa: Piao, C., Dutkiewicz, E., Kollipara, L., Sickmann, A., Huang, S., &#38; Sigrist,
    S. J. (2026). Active zone plasticity couples sleep need to presynaptic hypophosphorylation.
    <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences.
    <a href="https://doi.org/10.1073/pnas.2524065123">https://doi.org/10.1073/pnas.2524065123</a>
  chicago: Piao, Chengji, Ewelina Dutkiewicz, Laxmikanth Kollipara, Albert Sickmann,
    Sheng Huang, and Stephan J. Sigrist. “Active Zone Plasticity Couples Sleep Need
    to Presynaptic Hypophosphorylation.” <i>Proceedings of the National Academy of
    Sciences</i>. National Academy of Sciences, 2026. <a href="https://doi.org/10.1073/pnas.2524065123">https://doi.org/10.1073/pnas.2524065123</a>.
  ieee: C. Piao, E. Dutkiewicz, L. Kollipara, A. Sickmann, S. Huang, and S. J. Sigrist,
    “Active zone plasticity couples sleep need to presynaptic hypophosphorylation,”
    <i>Proceedings of the National Academy of Sciences</i>, vol. 123, no. 24. National
    Academy of Sciences, 2026.
  ista: Piao C, Dutkiewicz E, Kollipara L, Sickmann A, Huang S, Sigrist SJ. 2026.
    Active zone plasticity couples sleep need to presynaptic hypophosphorylation.
    Proceedings of the National Academy of Sciences. 123(24), e2524065123.
  mla: Piao, Chengji, et al. “Active Zone Plasticity Couples Sleep Need to Presynaptic
    Hypophosphorylation.” <i>Proceedings of the National Academy of Sciences</i>,
    vol. 123, no. 24, e2524065123, National Academy of Sciences, 2026, doi:<a href="https://doi.org/10.1073/pnas.2524065123">10.1073/pnas.2524065123</a>.
  short: C. Piao, E. Dutkiewicz, L. Kollipara, A. Sickmann, S. Huang, S.J. Sigrist,
    Proceedings of the National Academy of Sciences 123 (2026).
date_created: 2026-08-18T10:46:33Z
date_published: 2026-06-16T00:00:00Z
date_updated: 2026-08-20T05:35:33Z
day: '16'
ddc:
- '570'
doi: 10.1073/pnas.2524065123
extern: '1'
external_id:
  pmid:
  - '42258713'
file:
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  creator: dernst
  date_created: 2026-08-20T05:34:25Z
  date_updated: 2026-08-20T05:34:25Z
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  file_name: 2026_PNAS_Piao.pdf
  file_size: 3915000
  relation: main_file
  success: 1
file_date_updated: 2026-08-20T05:34:25Z
has_accepted_license: '1'
intvolume: '       123'
issue: '24'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '06'
oa: 1
oa_version: Published Version
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'
scopus_import: '1'
status: public
title: Active zone plasticity couples sleep need to presynaptic hypophosphorylation
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 123
year: '2026'
...