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PXD041205

PXD041205 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleQuantitative proteomic analysis reveals apoE4-dependent phosphorylation of the actin regulating protein VASP
DescriptionApolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer’s Disease (AD). While neurons generally produce a minority of the apoE in the central nervous system, neuronal expression of apoE increases dramatically in response to stress and is sufficient to drive pathology. Currently, the molecular mechanisms of how apoE4 expression may regulate pathology are not fully understood. Here we expand upon our previous studies measuring the impact of apoE4 on protein abundance to include the analysis of protein phosphorylation and ubiquitylation signaling in isogenic Neuro-2a cells expressing apoE3 or apoE4. We find that apoE4 expression results in the dramatic increase in VASP S235 phosphorylation in a PKA-dependent manner. This phosphorylation results in the loss of VASP interactions with numerous actin cytoskeletal and microtubular proteins. Reduction of VASP S235 phosphorylation via PKA inhibition results in a significant increase in filopodia formation and neurite outgrowth in apoE4-expressing cells to levels beyond that of apoE3. Our results highlight the pronounced and diverse impact of apoE4 on multiple modes of protein regulation and identify potential therapeutic targets to restore apoE4-related cytoskeletal defects.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:44:42.291.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDanielle Swaney
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListubiquitinylated lysine; phosphorylated residue
InstrumentOrbitrap Fusion Lumos; Orbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-03-30 03:58:22ID requested
12023-04-07 22:11:26announced
22023-11-14 08:44:50announced2023-11-14: Updated project metadata.
Publication List
Cakir Z, Lord SJ, Zhou Y, Jang GM, Polacco BJ, Eckhardt M, Jimenez-Morales D, Newton BW, Orr AL, Johnson JR, da Cruz A, Mullins RD, Krogan NJ, Mahley RW, Swaney DL, Quantitative Proteomic Analysis Reveals apoE4-Dependent Phosphorylation of the Actin-Regulating Protein VASP. Mol Cell Proteomics, 22(5):100541(2023) [pubmed]
Keyword List
submitter keyword: ubiquitylation, PPIs,Alzheimer's Disease, phosphorylation
Contact List
Danielle Swaney
contact affiliationUCSF
contact emaildaniswan@gmail.com
lab head
Danielle Swaney
contact affiliationUCSF
contact emaildaniswan@gmail.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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