Evidence map›Paper›PMID 34269176›Full record

ArticleeLife2021

Action potential-coupled Rho GTPase signaling drives presynaptic plasticity.

Shataakshi Dube O'Neil, Bence Rácz, Walter Evan Brown, Yudong Gao, Erik J Soderblom, Ryohei Yasuda, Scott H Soderling

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
  2. Article
  3. Disruption of a selective vesicle pool upon retrograde amnesia dissociates memory at presynaptic terminals.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Deciphering the Nanoscale Architecture of Presynaptic Actin Using a Micropatterned Presynapse-on-Glass Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Presynaptic Rac1 in the hippocampus selectively regulates working memory.bioRxiv : the preprint server for biology · 2024
    Article
  18. Review
  19. Article
  20. Presynapses contain distinct actin nanostructures.The Journal of cell biology · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Shataakshi Dube O'NeilDepartment of Neurobiology, Duke University Medical Center, Durham, United States.ORCID 0000-0002-5888-4270
Bence RáczDepartment of Anatomy and Histology, University of Veterinary Medicine, Budapest, Hungary.
Walter Evan BrownDepartment of Cell Biology, Duke University Medical Center, Durham, United States.
Yudong GaoDepartment of Cell Biology, Duke University Medical Center, Durham, United States.
Erik J SoderblomDepartment of Cell Biology, Duke University Medical Center, Durham, United States.
Ryohei YasudaMax Planck Florida Institute for Neuroscience, Jupiter, United States.ORCID 0000-0001-6263-9297
Scott H SoderlingDepartment of Neurobiology, Duke University Medical Center, Durham, United States.ORCID 0000-0001-7808-197X
Duke University · USMax Planck Florida Institute for Neuroscience · USUniversity of Veterinary Medicine · HU

Funding

Neuronal Intracellular Signaling Underlying Synaptic, Circuit and Behavioral PlasticityR35NS116804 · NINDS · MAX PLANCK FLORIDA CORPORATION · PI Ryohei Yasuda · 2020 to 2026
$7.8M
Mechanisms of Ras Signaling in Single SynapsesR01MH080047 · NIMH · MAX PLANCK FLORIDA CORPORATION · PI YASUDA, RYOHEI · 2007 to 2023
$6.8M
Molecular Analysis of Developmental Brain Disorders Associated with Synaptic PathologyR01MH111684 · NIMH · DUKE UNIVERSITY · PI SCOTT H SODERLING · 2017 to 2026
$6.6M
Proteomic and Functional Analysis of Presynaptic Physiology and PlasticityR01MH126954 · NIMH · DUKE UNIVERSITY · PI SODERLING, SCOTT H · 2021 to 2025
$2.9M
Analysis of Inhibitory Synaptic Proteins Associated with Brain DisordersR01NS102456 · NINDS · DUKE UNIVERSITY · PI SODERLING, SCOTT H · 2017 to 2021
$2.6M
NIMH NIH HHS R01 MH080047NIMH NIH HHS R01 MH111684NIMH NIH HHS R01 MH126954NINDS NIH HHS R01 NS102456NINDS NIH HHS R35 NS116804
6 · The paper itself

Abstract

In contrast to their postsynaptic counterparts, the contributions of activity-dependent cytoskeletal signaling to presynaptic plasticity remain controversial and poorly understood. To identify and evaluate these signaling pathways, we conducted a proteomic analysis of the presynaptic cytomatrix using in vivo biotin identification (iBioID). The resultant proteome was heavily enriched for actin cytoskeleton regulators, including Rac1, a Rho GTPase that activates the Arp2/3 complex to nucleate branched actin filaments. Strikingly, we find Rac1 and Arp2/3 are closely associated with synaptic vesicle membranes in adult mice. Using three independent approaches to alter presynaptic Rac1 activity (genetic knockout, spatially restricted inhibition, and temporal optogenetic manipulation), we discover that this pathway negatively regulates synaptic vesicle replenishment at both excitatory and inhibitory synapses, bidirectionally sculpting short-term synaptic depression. Finally, we use two-photon fluorescence lifetime imaging to show that presynaptic Rac1 activation is coupled to action potentials by voltage-gated calcium influx. Thus, this study uncovers a previously unrecognized mechanism of actin-regulated short-term presynaptic plasticity that is conserved across excitatory and inhibitory terminals. It also provides a new proteomic framework for better understanding presynaptic physiology, along with a blueprint of experimental strategies to isolate the presynaptic effects of ubiquitously expressed proteins.

Indexed as

ProteomicsActin CytoskeletonActinsAction PotentialsAnimalsCalciumCytoskeletonHippocampusMiceNeuronal PlasticityNeuropeptidesrac1 GTP-Binding Proteinrho GTP-Binding ProteinsSynapsesSynaptic VesiclesActinsCalciumNeuropeptidesrac1 GTP-Binding ProteinRac1 protein, mouserho GTP-Binding Proteins2pFLIMcell biologycytoskeletonmouseneurosciencepresynapseproteomicsRac1short-term plasticity

Identifiers

PMID34269176
PMCPMC8285108
OpenAlexW3179441771

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.