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PXD017270

PXD017270 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIdentification of palmitoyl protein thioesterase 1 substrates defines roles for synaptic depalmitoylation
DescriptionWe 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:36:25.665.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTuKiet Lam
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-01-23 06:21:08ID requested
12022-05-19 06:00:30announced
22024-10-22 05:36:26announced2024-10-22: Updated project metadata.
Publication List
10.1371/journal.pbio.3001590;
Gorenberg EL, Massaro Tieze S, Y, ΓΌ, 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]
Keyword List
submitter keyword: synapse, synaptic cleft, synaptic vesicle endocytosis, neuronal ceroid lipofuscinoisis, synaptic adhesion molecules, AMPA receptor, neurodegeneration,palmitoylation, Palmitoyl protein thioesterase 1
Contact List
TuKiet Lam
contact affiliationDepartment of Molecular Biophysics and Biochemistry, Yale University, Keck MS & Proteomics Resource at Yale.
contact emailtukiet.lam@yale.edu
lab head
TuKiet Lam
contact affiliationYale University
contact emailtukiet.lam@yale.edu
dataset submitter
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Dataset FTP location
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