PXD029429

PXD029429 is an original dataset announced via ProteomeXchange.

Title	TREM2 interacts with TDP-43 and mediates microglial neuroprotection against TDP-43-related neurodegeneration
Description	Triggering receptor expressed on myeloid cell 2 (TREM2) is linked to neurodegenerative disease risk. However, the function of TREM in neurodegeneration is still unclear. Here we investigated the role of microglial TREM2 in TAR-DNA binding protein 43 kDa (TDP-43)-related neurodegeneration using viral-mediated and transgenic mouse models. We found that TREM2 deficiency impaired phagocytic clearance of pathological TDP-43 by microglia, and enhanced neuronal damage and motor impairments. Mass cytometry analysis revealed that hTDP-43 induced a TREM2-dependent subpopulation of microglia with high CD11c expression and phagocytic ability. Using mass spectrometry and surface plasmon resonance analysis, we further demonstrated an interaction between TDP-43 and TREM2 in vitro and in vivo as well as in ALS patient tissues. We computationally identified the region within hTDP-43 that interacts with TREM2. Our data highlights that TDP-43 is a possible ligand for microglial TREM2 and that this interaction mediates neuroprotection effects of microglia in TDP-43-related neurodegeneration.
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-11_23:53:16.109.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD029429
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Long-Jun Wu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Exploris 480; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-29 04:26:14	ID requested
⏵ 1	2022-08-11 23:53:16	announced

Xie M, Liu YU, Zhao S, Zhang L, Bosco DB, Pang YP, Zhong J, Sheth U, Martens YA, Zhao N, Liu CC, Zhuang Y, Wang L, Dickson DW, Mattson MP, Bu G, Wu LJ, TREM2 interacts with TDP-43 and mediates microglial neuroprotection against TDP-43-related neurodegeneration. Nat Neurosci, 25(1):26-38(2022) [pubmed]

submitter keyword: Human, Mouse, LC-MS/MS

Long-Jun Wu
contact affiliation	Departments of Neurology and Neuroscience Mayo Clinic, Rochester, MN, USA
contact email	wu.longjun@mayo.edu
lab head
Long-Jun Wu
contact affiliation	Mayo Clinic
contact email	wu.longjun@mayo.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029429
     1. Label: PRIDE project
     2. Name: TREM2 interacts with TDP-43 and mediates microglial neuroprotection against TDP-43-related neurodegeneration