PXD032052 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Identification of substrates of palmitoyl protein thioesterase 1 highlights roles of depalmitoylation in disulfide bond formation and synaptic function |
Description | 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 and mass spectrometry to identify proteins with increased in vivo palmitoylation in PPT1 knockout 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 post-translational modifications. 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. |
HostingRepository | PRIDE |
AnnounceDate | 2022-03-23 |
AnnouncementXML | Submission_2022-03-23_14:34:37.225.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; acetylated residue; iodoacetamide derivatized residue; deamidated residue |
Instrument | Q Exactive Plus |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-03-03 12:23:45 | ID requested | |
1 | 2022-03-06 20:19:07 | announced | |
⏵ 2 | 2022-03-23 14:34:37 | announced | 2022-03-23: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: synapse, synaptic vesicle endocytosis, neuronal ceroid lipofuscinosis, Na+/K+ transporting ATPase, palmitoyl protein thioesterase 1, synaptic adhesion molecules, ZDHHC, neurodegeneration,palmitoylation, disulfide bond |
Contact List
TuKiet Lam |
contact affiliation | Yale University (Keck MS & Proteomics Resource) |
contact email | tukiet.lam@yale.edu |
lab head | |
TuKiet Lam |
contact affiliation | Yale University |
contact email | tukiet.lam@yale.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD032052
- Label: PRIDE project
- Name: Identification of substrates of palmitoyl protein thioesterase 1 highlights roles of depalmitoylation in disulfide bond formation and synaptic function