Evidence map›Paper›PMID 35358180›Full record

ArticlePLoS biology2022

Identification of substrates of palmitoyl protein thioesterase 1 highlights roles of depalmitoylation in disulfide bond formation and synaptic function.

Erica L Gorenberg, Sofia Massaro Tieze, Betül Yücel, Helen R Zhao, Vicky Chou, Gregory S Wirak, Susumu Tomita, TuKiet T Lam, Sreeganga S Chandra

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
5.4field-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

35 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
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  8. Review
  9. The Roles of ProteinCancer communications (London, England) · 2026
    Review
  10. Article
  11. Article
  12. Article
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  14. PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  15. Review
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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

9 authors at 2 institutions in 1 country.

Erica L GorenbergDepartments of Neurology and Neuroscience, Yale University, New Haven, Connecticut, United States of America.ORCID 0000-0003-0542-3793
Sofia Massaro TiezeDepartments of Neurology and Neuroscience, Yale University, New Haven, Connecticut, United States of America.ORCID 0000-0001-7545-411X
Betül YücelDepartments of Neurology and Neuroscience, Yale University, New Haven, Connecticut, United States of America.
Helen R ZhaoDepartments of Neurology and Neuroscience, Yale University, New Haven, Connecticut, United States of America.
Vicky ChouDepartments of Neurology and Neuroscience, Yale University, New Haven, Connecticut, United States of America.
Gregory S WirakDepartments of Neurology and Neuroscience, Yale University, New Haven, Connecticut, United States of America.ORCID 0000-0001-9645-1882
Susumu TomitaDepartments of Neuroscience and of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut, United States of America.
TuKiet T LamDepartments of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, United States of America.
Sreeganga S ChandraDepartments of Neurology and Neuroscience, Yale University, New Haven, Connecticut, United States of America.
Yale University · USW. M. Keck Foundation · US

Funding

Yale/NIDA Neuroproteomics Research CenterP30DA018343 · NIDA · YALE UNIVERSITY · PI ANGUS C. NAIRN, Kenneth Robert WILLIAMS · 2004 to 2026
$37.1M
Interdepartmental Neuroscience Program (INP)T32NS041228 · NINDS · YALE UNIVERSITY · PI Charles A Greer, Marina R Picciotto · 2001 to 2026
$12.0M
Regulation of glutamate receptors by calcium-dependent protein kinasesR01MH077939 · NIMH · YALE UNIVERSITY · PI TOMITA, SUSUMU · 2008 to 2023
$5.2M
NEUROBIOLOGY OF CORTICAL SYSTEMST32NS007224 · NINDS · YALE UNIVERSITY · PI CARDIN, JESSICA A · 1985 to 2025
$4.6M
Role of Glucosylsphingosine in Parkinson Disease and Dementia with Lewy BodiesRF1NS110354 · NINDS · YALE UNIVERSITY · PI CHANDRA, SREEGANGA S · 2019 to 2022
$2.5M
Roles of the CSPalpha Chaperone Complex in Presynaptic Maintenance and ANCLR01NS083846 · NINDS · YALE UNIVERSITY · PI CHANDRA, SREEGANGA S · 2014 to 2018
$2.2M
The Physiological Functions of SynucleinsR01NS064963 · NINDS · YALE UNIVERSITY · PI CHANDRA, SREEGANGA S · 2010 to 2014
$1.6M
6500 QTrap Mass Spectrometer for Yale UniversityS10OD018034 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2014 to 2014
$514k
Identifying the neuronal substrates of the depalmitoylating enzyme PPT1R21NS094971 · NINDS · YALE UNIVERSITY · PI CHANDRA, SREEGANGA S · 2016 to 2017
$460k
NIDA NIH HHS P30 DA018343NIH HHS S10 OD018034NIMH NIH HHS R01 MH077939NINDS NIH HHS R01 NS064963NINDS NIH HHS R01 NS083846NINDS NIH HHS R21 NS094971NINDS NIH HHS RF1 NS110354NINDS NIH HHS T32 NS007224NINDS NIH HHS T32 NS041228
6 · The paper itself

Abstract

Loss-of-function mutations in the depalmitoylating enzyme palmitoyl protein thioesterase 1 (PPT1) cause neuronal ceroid lipofuscinosis (NCL), a devastating neurodegenerative disease. The substrates of PPT1 are largely undescribed, posing a limitation on molecular dissection of disease mechanisms and therapeutic development. Here, we provide a resource identifying >100 novel PPT1 substrates. We utilized Acyl Resin-Assisted Capture (Acyl RAC) and mass spectrometry to identify proteins with increased in vivo palmitoylation in PPT1 knockout (KO) mouse brains. We then validated putative substrates through direct depalmitoylation with recombinant PPT1. This stringent screen elucidated diverse PPT1 substrates at the synapse, including channels and transporters, G-protein-associated molecules, endo/exocytic components, synaptic adhesion molecules, and mitochondrial proteins. Cysteine depalmitoylation sites in transmembrane PPT1 substrates frequently participate in disulfide bonds in the mature protein. We confirmed that depalmitoylation plays a role in disulfide bond formation in a tertiary screen analyzing posttranslational modifications (PTMs). Collectively, these data highlight the role of PPT1 in mediating synapse functions, implicate molecular pathways in the etiology of NCL and other neurodegenerative diseases, and advance our basic understanding of the purpose of depalmitoylation.

Indexed as

Neuronal Ceroid-LipofuscinosesAnimalsDisulfidesLipoylationMiceMice, KnockoutSynapsesDisulfides

Identifiers

PMID35358180
PMCPMC9004782
OpenAlexW4220848594

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.