Evidence map›Paper›PMID 38128479›Full record

ArticleNeuron2023

Serine-129 phosphorylation of α-synuclein is an activity-dependent trigger for physiologic protein-protein interactions and synaptic function.

Leonardo A Parra-Rivas, Kayalvizhi Madhivanan, Brent D Aulston, Lina Wang, Dube Dheeraj Prakashchand, Nicholas P Boyer, Veronica M Saia-Cereda, Kristen Branes-Guerrero, Donald P Pizzo, Pritha Bagchi and 7 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
24.1field-weighted citation impact, top 1% 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

91 citing papers in PubMed, 117 citations in OpenAlex.

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31 more citing papers are in PubMed but not listed here.

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

17 authors at 3 institutions in 1 country.

Leonardo A Parra-RivasDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
Kayalvizhi MadhivananDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
Brent D AulstonDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
Lina WangDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
Dube Dheeraj PrakashchandDepartment of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA, USA.
Nicholas P BoyerDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
Veronica M Saia-CeredaDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
Kristen Branes-GuerreroDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
Donald P PizzoDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
Pritha BagchiEmory Integrated Proteomics Core, Emory University, Atlanta, GA, USA.
V S SundarDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
Yong TangDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
Utpal DasDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA; Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
David A ScottDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
Padmini RangamaniDepartment of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA, USA.
Yuki OgawaDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Subhojit RoyDepartment of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA; Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA. Electronic address: sroy@ucsd.edu.
University of California San Diego · USBaylor College of Medicine · USEmory University · US

Funding

Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Pathophysiologic roles of alpha-synuclein at the synapseR01NS111978 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROY, SUBHOJIT · 2019 to 2023
$2.4M
JEOL JEM-1400Plus Transmission Electron MicroscopeS10OD023527 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FARQUHAR, MARILYN GIST · 2017 to 2017
$579k
NCATS NIH HHS UL1 TR002378NIH HHS S10 OD023527NINDS NIH HHS P30 NS047101NINDS NIH HHS R01 NS111978
6 · The paper itself

Abstract

Phosphorylation of α-synuclein at the serine-129 site (α-syn Ser129P) is an established pathologic hallmark of synucleinopathies and a therapeutic target. In physiologic states, only a fraction of α-syn is phosphorylated at this site, and most studies have focused on the pathologic roles of this post-translational modification. We found that unlike wild-type (WT) α-syn, which is widely expressed throughout the brain, the overall pattern of α-syn Ser129P is restricted, suggesting intrinsic regulation. Surprisingly, preventing Ser129P blocked activity-dependent synaptic attenuation by α-syn-thought to reflect its normal function. Exploring mechanisms, we found that neuronal activity augments Ser129P, which is a trigger for protein-protein interactions that are necessary for mediating α-syn function at the synapse. AlphaFold2-driven modeling and membrane-binding simulations suggest a scenario where Ser129P induces conformational changes that facilitate interactions with binding partners. Our experiments offer a new conceptual platform for investigating the role of Ser129 in synucleinopathies, with implications for drug development.

Indexed as

Parkinson DiseaseSynucleinopathiesalpha-SynucleinHumansPhosphorylationSerinealpha-SynucleinSerinealanine mutationsAlphaFoldCRISPRendogenous taggingneuronal activitypHluorinproximity-ligation assayserine phosphorylationsynapsesα-synuclein

Identifiers

PMID38128479
PMCPMC10766085
OpenAlexW4389992959

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.