PXD017270

PXD017270 is an original dataset announced via ProteomeXchange.

Title	Identification of palmitoyl protein thioesterase 1 substrates defines roles for synaptic depalmitoylation
Description	We report here the identification of substrates of the depalmitoylating enzyme PPT1 by quantitative mass spectrometry. We utilized a stringent two-step Acyl Resin-Assisted Capture (Acyl RAC) screen in which increased palmitoylation in vivo in PPT1 knockout is the first selection criteria for substrates. We validated hits by direct depalmitoylation with PPT1 to identify bona fide substrates. Most proteins identified are previously reported to be palmitoylated and the few known PPT1 substrates were validated. Significantly, the screen identified >100 proteins not previously known to be depalmitoylated by PPT1, including a wide range of endocytic, signaling, synaptic adhesion, mitochondrial, and lysosomal proteins. These proteins collectively explain the many facets of CLN1 disease caused by the loss of PPT1 function. We determined that an Ig domain in synaptic adhesion molecules may be a PPT1 recognition site for depalmitoylation. Finally, we provide evidence that PPT1 participates in neuronal activity-dependent palmitoylation-depalmitoylation cycles at the synapse.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:36:25.665.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	TuKiet Lam
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-23 06:21:08	ID requested
1	2022-05-19 06:00:30	announced
⏵ 2	2024-10-22 05:36:26	announced	2024-10-22: Updated project metadata.

10.1371/journal.pbio.3001590;

Gorenberg EL, Massaro Tieze S, Y, ü, cel B, Zhao HR, Chou V, Wirak GS, Tomita S, Lam TT, Chandra SS, highlights roles of depalmitoylation in disulfide bond formation and synaptic function. PLoS Biol, 20(3):e3001590(2022) [pubmed]

submitter keyword: synapse, synaptic cleft, synaptic vesicle endocytosis, neuronal ceroid lipofuscinoisis, synaptic adhesion molecules, AMPA receptor, neurodegeneration,palmitoylation, Palmitoyl protein thioesterase 1

TuKiet Lam
contact affiliation	Department of Molecular Biophysics and Biochemistry, Yale University, Keck MS & Proteomics Resource at Yale.
contact email	tukiet.lam@yale.edu
lab head
TuKiet Lam
contact affiliation	Yale University
contact email	tukiet.lam@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017270
     1. Label: PRIDE project
     2. Name: Identification of palmitoyl protein thioesterase 1 substrates defines roles for synaptic depalmitoylation