Selective regulation of aspartyl intramembrane protease activity by calnexin.
Calnexin
ER quality control
Intramembrane proteolysis
Male reproduction
Protease regulation
SPPL2c
Signal peptide peptidase
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
26 Oct 2024
26 Oct 2024
Historique:
received:
12
06
2024
accepted:
11
10
2024
revised:
09
09
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
26
10
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39460794
doi: 10.1007/s00018-024-05478-8
pii: 10.1007/s00018-024-05478-8
doi:
Substances chimiques
Calnexin
139873-08-8
Aspartic Acid Endopeptidases
EC 3.4.23.-
Aspartic Acid Proteases
EC 3.4.-
signal peptide peptidase
EC 3.4.23.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
441Informations de copyright
© 2024. The Author(s).
Références
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