PXD059716-1

PXD059716 is an original dataset announced via ProteomeXchange.

Title	Proteomics of tau repeat domain interactome via split TurboID proximity labeling
Description	In Alzheimer's disease (AD) and other tauopathies, tau dissociates from microtubules and forms toxic aggregates that contribute to neurodegeneration. Although some of the pathological interactions of tau have been identified from postmortem brain tissue, these studies are limited by their inability to capture transient interactions. To investigate the interactome of aggregate-prone fragments of tau, we applied an in vitro proximity labeling technique using split TurboID fused with the tau microtubule repeat domain (TauRD), a core region implicated in tau aggregation. We characterized this split TurboID TauRD displaying the requirement for both ligase fragment co-expression for robust enzyme activity and nuclear and cytoplasmic localization of the recombinant proteins. Following enrichment of biotinylated proteins and mass spectrometry, we identified over 700 TauRD interactors. Gene ontology analysis of enriched TauRD interactors highlighted processes often dysregulated in tauopathies, including spliceosome complexes, RNA-binding proteins (RBPs), and nuclear speckles. These in vitro results were further supported by integrating the TauRD interactome data with human AD tau interactome datasets and protein co-expression networks from human AD and related tauopathies. This revealed an overlap with the in vitro TauRD interactome and several modules enriched with RBPs and increased in AD and PSP. These findings emphasize the importance of nuclear pathways in tau pathology, such as RNA splicing and nuclear-cytoplasmic transport and establishes the sTurbo TauRD system as a valuable tool for exploring the tau interactome.
HostingRepository	PRIDE
AnnounceDate	2025-11-12
AnnouncementXML	Submission_2025-11-12_08:33:34.139.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eddie Fox
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-13 00:50:56	ID requested
⏵ 1	2025-11-12 08:33:35	announced

Shapley SM, Shantaraman A, Gadhavi J, Kearney MA, Dammer EB, Duong DM, Bowen CA, Watson CM, Bagchi P, Guo Q, Rangaraju S, Seyfried NT, Proximity Labeling of the Tau Repeat Domain Enriches RNA-Binding Proteins That Are Altered in Alzheimer's Disease and Related Tauopathies. Mol Cell Proteomics, 25(1):101458(2025) [pubmed]

10.1016/j.mcpro.2025.101458;

submitter keyword: Alzheimer’s Disease, MSFragger, Tau, Proximity Labeling, LFQ, Proteomics

Nicholas T.
contact affiliation	Emory University School of Medicine Departments of Biochemistry and Neurology
contact email	nseyfri@emory.edu
lab head
Eddie Fox
contact affiliation	Emory University
contact email	ejfox2@emory.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059716
     1. Label: PRIDE project
     2. Name: Proteomics of tau repeat domain interactome via split TurboID proximity labeling