PXD052965

PXD052965 is an original dataset announced via ProteomeXchange.

Title	Selective regulation of aspartyl intramembrane protease activity by calnexin
Description	Signal peptide peptidase-like 2c (SPPL2c) is a testis-specific aspartyl intramembrane protease that contributes to male gamete function both by catalytic and non-proteolytic mechanisms. Here, we provide an unbiased characterisation of the in vivo interactome of SPPL2c identifying the ER chaperone calnexin as novel binding partner of this enzyme. Recruitment of calnexin specifically required the N-glycosylation within the N-terminal protease-associated domain of SPPL2c. Importantly, mutation of the single glycosylation site of SPPL2c or loss of calnexin expression completely prevented SPPL2c-mediated intramembrane proteolysis of all tested substrates. By contrast and despite rather promiscuous binding of calnexin to other SPP/SPPL proteases, expression of the chaperone was exclusively required for SPPL2c-mediated proteolysis. Despite some impact on the stability of SPPL2c most presumably due to assistance in folding of the luminal domain of the protease, calnexin appeared to be recruited rather constitutively to the protease thereby boosting its catalytic activity. In summary, we describe a novel, highly specific mode of intramembrane protease regulation, highlighting the need to systematically approach control mechanisms governing the proteolytic activity of other members of the aspartyl intramembrane protease family.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-06_18:36:00.845.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marc Gentzel
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-10 09:09:07	ID requested
⏵ 1	2025-05-06 18:36:01	announced

Contreras W, Groenendyk J, Gentzel M, Sch, ö, nberg PY, Buchholz F, Michalak M, Schr, ö, der B, Mentrup T, Selective regulation of aspartyl intramembrane protease activity by calnexin. Cell Mol Life Sci, 81(1):441(2024) [pubmed]

10.1007/s00018-024-05478-8;

submitter keyword: Co-IP,Signal Peptide Peptidase-Like 2c, Mouse, Calnexin, SPPL2C, Testis

Torben Mentrup
contact affiliation	Institute of Physiological Chemistry, Technische UniversitŠt Dresden, Dresden, Germany
contact email	torben.mentrup@tu-dresden.de
lab head
Marc Gentzel
contact affiliation	Molecular Analysis - Mass Spectrometry, Center for Molecular and Cellular Bioengineering (CMCB), TU Dresden
contact email	marc.gentzel@tu-dresden.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052965
     1. Label: PRIDE project
     2. Name: Selective regulation of aspartyl intramembrane protease activity by calnexin