PXD026306

PXD026306 is an original dataset announced via ProteomeXchange.

Title	Tau interactome mapping reveals dynamic processes associated with neurodegenerative diseases
Description	The Tau (MAPT) protein drives neuronal dysfunction and toxicity in the brain in Alzheimer’s disease (AD) and other Tauopathies. To dissect the complexity of the Tau interactome that underlies this process we used two proteomic approaches to characterize the dynamic and multifaceted nature of Tau protein-protein interactions in human induced pluripotent stem cell (iPSC)-derived neurons. We used engineered ascorbic acid peroxidase (APEX) for spatiotemporally restricted mapping of Tau interaction proteins in combination with quantitative affinity purification mass spectrometry (AP-MS) to interrogate disease-related changes in the Tau interactome. The APEX method resolved subcellular interactions of wild-type Tau at amino acid level resolution in living neurons as well as novel activity-dependent interactions of Tau with presynaptic vesicle proteins that occurred during Tau secretion from neurons. Among the many Tau interacting proteins revealed by AP-MS, the interaction of mitochondrial proteins with wild-type Tau (TauWT) was more robust than with TauV337M or TauP301L. The mitochondrial proteins that preferentially interacted with TauWT comprised a protein module that is downregulated in multi-omics analyses of human AD brains. Mitochondrial bioenergetics were altered in TauV337M compared to TauWT human iPSC-derived neurons confirming the impact of Tau on mitochondria. These Tau interactome analyses open up novel disease-related processes as potential therapeutic targets to block Tau-mediated pathogenesis.
HostingRepository	PRIDE
AnnounceDate	2022-01-11
AnnouncementXML	Submission_2022-01-10_22:45:39.301.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Danielle Swaney
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue
Instrument	Orbitrap Fusion Lumos; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-27 02:37:39	ID requested
⏵ 1	2022-01-10 22:45:39	announced

Dataset with its publication pending

submitter keyword: Tau, APEX, PPI

Nevan Krogan
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. PXD026306
     1. Label: PRIDE project
     2. Name: Tau interactome mapping reveals dynamic processes associated with neurodegenerative diseases