PXD059099-1

PXD059099 is an original dataset announced via ProteomeXchange.

Title	TECPR2 knock-in mice proteomics
Description	Mutation in the gene encoding Tectonic -propeller repeat-containing repeat protein 2 (TECPR2) leads to hereditary sensory and autonomic neuropathy type 9 (HSAN9) which is a fatal complex neurodevelopmental and neurodegenerative disorder involving the sensory and peripheral nervous system. TECPR2 is linked to trafficking and sorting of proteins within the cell, however, its functional role remains poorly defined. Furthermore, molecular insights into pathogenic mechanisms underlying HSAN9 are lacking. Here, we report a mouse model which harbors a HSAN9-associated nonsense mutation that causes loss of TECPR2 expression. These mice show altered gait, region-specific axonal dystrophy with accumulating membrane-bound structures and extensive gliosis. Transcriptomics, cerebrospinal fluid proteomics and microglia proteome profiling point to damage-associated microglia with a dysfunctional endolysosomal system. The latter was confirmed in cellular assays and linked to TECPR2’s interaction with the membrane-tethering complex HOPS. Collectively, we uncovered a role of TECPR2 in endolysosome maintenance which seems relevant for microglia and neurons.
HostingRepository	PRIDE
AnnounceDate	2025-11-10
AnnouncementXML	Submission_2025-11-09_17:33:35.336.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Behrends
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	carbamoylated residue; acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-20 07:07:18	ID requested
⏵ 1	2025-11-09 17:33:36	announced

10.1038/s41419-025-08168-w;

Bhattacharya D, da Silva-Buttkus P, Nalbach K, Cheng L, Garrett L, Irmler M, Kislinger G, Werner G, Rodde R, Lengger C, Beckers J, Zimprich A, H, ö, lter SM, Gailus-Durner V, Fuchs H, Hrabe de Angelis M, Wefers B, Wurst W, Brill MS, Schifferer M, Lichtenthaler SF, Behrends C, Neuropathy-associated Tecpr2 mutation knock-in mice reveal endolysosomal loss of function phenotypes in neurons and microglia. Cell Death Dis, 16(1):775(2025) [pubmed]

submitter keyword: BiCAP, EndoIP, HSAN9, microglia,TECPR2

Christian Behrends
contact affiliation	Munich Cluster for Systems Neurology (SyNergy Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
contact email	christian.behrends@mail03.med.uni-muenchen.de
lab head
Christian Behrends
contact affiliation	SyNergy, LMU München
contact email	christian.behrends@mail03.med.uni-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059099
     1. Label: PRIDE project
     2. Name: TECPR2 knock-in mice proteomics