PXD030354

PXD030354 is an original dataset announced via ProteomeXchange.

Title	The Transglutaminase-2 interactome in the APP23 mouse model of Alzheimer disease
Description	Amyloid-beta (Aβ) deposition in the brain, is closely linked to development of Alzheimer’s disease (AD). Unfortunately, therapies specifically targeting Aβ deposition have failed to reach their primary clinical endpoints, emphasizing the need to broaden the search strategy for identification of alternative therapeutic targets/mechanisms. Transglutaminase (TG2) catalyses posttranslational modifications, is present in characteristic AD lesions and has AD-associated proteins, including Aβ, tau and apolipoprotein E. However, an unbiased overview of TG2 interactors (TG2 interactome) and the cellular pathways of which these interactors are part in control and AD brain is lacking. Here, anticipating future studies in AD brain, we aimed to identify these interactors and their pathways using a crossbred of the AD-mimicking APP23 mouse model with wildtype and TG2-/- mice. We found that absence of TG2 had no (statistically) significant effect on Aβ pathology, soluble brain levels of Aβ1-40, Aβ1-42, and mRNA levels of TG2 family members compared to APP23 mice. Quantitative proteomics and network analysis revealed a large cluster of TG2 interactors with synaptic transmission/assembly and cell adhesion typical of AD in the APP23 brain. Comparative proteomics were in line with these observations as it also revealed association of proteins of both pathways to be linked to TG2 in APP23 brains Together, our data showed that TG2 deletion led to considerable network alterations consistent with a role of TG2 in (dys)regulation of synaptic transmission and cell adhesion in APP23 brains.
HostingRepository	PRIDE
AnnounceDate	2022-02-22
AnnouncementXML	Submission_2022-02-22_04:22:03.213.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Boocock
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-13 03:06:21	ID requested
⏵ 1	2022-02-22 04:22:04	announced

Wilhelmus MMM, Tonoli E, Coveney C, Boocock DJ, Jongenelen CAM, Brev, é JJP, Verderio EAM, Drukarch B, The Transglutaminase-2 Interactome in the APP23 Mouse Model of Alzheimer's Disease. Cells, 11(3):(2022) [pubmed]

submitter keyword: LC-MSMS SWATH Mouse TGM2 Alzheimer's

David Boocock
contact affiliation	John van Geest Cancer Research Centre, Nottingham Trent University
contact email	david.boocock@ntu.ac.uk
lab head
David Boocock
contact affiliation	Nottingham Trent University
contact email	david.boocock@ntu.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030354
     1. Label: PRIDE project
     2. Name: The Transglutaminase-2 interactome in the APP23 mouse model of Alzheimer disease