PXD041205

PXD041205 is an original dataset announced via ProteomeXchange.

Title	Quantitative proteomic analysis reveals apoE4-dependent phosphorylation of the actin regulating protein VASP
Description	Apolipoprotein (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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:44:42.291.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Danielle Swaney
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	ubiquitinylated lysine; phosphorylated residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-30 03:58:22	ID requested
1	2023-04-07 22:11:26	announced
⏵ 2	2023-11-14 08:44:50	announced	2023-11-14: Updated project metadata.

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]

submitter keyword: ubiquitylation, PPIs,Alzheimer's Disease, phosphorylation

Danielle Swaney
contact affiliation	UCSF
contact email	daniswan@gmail.com
lab head
Danielle Swaney
contact affiliation	UCSF
contact email	daniswan@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041205
     1. Label: PRIDE project
     2. Name: Quantitative proteomic analysis reveals apoE4-dependent phosphorylation of the actin regulating protein VASP