The role of SPP/SPPL intramembrane proteases in membrane protein homeostasis.
SPPL proteases
atherosclerosis
autoimmunity
intramembrane proteolysis
membrane protein proteostasis
signal peptide peptidase
spermatogenesis
γ-secretase
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
25 Aug 2023
25 Aug 2023
Historique:
revised:
03
07
2023
received:
24
05
2023
accepted:
23
08
2023
pubmed:
26
8
2023
medline:
26
8
2023
entrez:
25
8
2023
Statut:
aheadofprint
Résumé
Signal peptide peptidase (SPP) and the four SPP-like proteases SPPL2a, SPPL2b, SPPL2c and SPPL3 constitute a family of aspartyl intramembrane proteases with homology to presenilins. The different members reside in distinct cellular localisations within the secretory pathway and the endo-lysosomal system. Despite individual cleavage characteristics, they all cleave single-span transmembrane proteins with a type II orientation exhibiting a cytosolic N-terminus. Though the identification of substrates is not complete, SPP/SPPL-mediated proteolysis appears to be rather selective. Therefore, according to our current understanding cleavage by SPP/SPPL proteases rather seems to serve a regulatory function than being a bulk proteolytic pathway. In the present review, we will summarise our state of knowledge on SPP/SPPL proteases and in particular highlight recently identified substrates and the functional and/or (patho)-physiological implications of these cleavage events. Based on this, we aim to provide an overview of the current open questions in the field. These are connected to the regulation of these proteases at the cellular level but also in context of disease and patho-physiological processes. Furthermore, the interplay with other proteostatic systems capable of degrading membrane proteins is beginning to emerge.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : 125440785/SFB877
Organisme : Deutsche Forschungsgemeinschaft
ID : 251390220/SCHR1284/1-2
Organisme : Deutsche Forschungsgemeinschaft
ID : 254872893/FL 635/2-3
Organisme : Deutsche Forschungsgemeinschaft
ID : 263531414/FOR 2290
Organisme : Deutsche Forschungsgemeinschaft
ID : 380321491/SCHR1284/2-1
Organisme : Deutsche Forschungsgemeinschaft
ID : 431664610/ME 5459/1-1
Informations de copyright
© 2023 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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