On the track of intramembrane clippers: the SPPL2a/b proteases caught in the act in animal models

0571441 - ÚOCHB 2024 GB eng J - Journal Article
Trávníčková, Květa - Stříšovský, Kvido
On the track of intramembrane clippers: the SPPL2a/b proteases caught in the act in animal models.
FEBS Journal. Roč. 290, č. 9 (2023), s. 2306-2310. ISSN 1742-464X. E-ISSN 1742-4658
R&D Projects: GA MŠMT(CZ) EF16_019/0000729
Institutional support: RVO:61388963
Keywords : intramembrane protease * proteolysis * signal peptide peptidase-like * SNARE * trafficking
OECD category: Biochemistry and molecular biology
Impact factor: 5.4, year: 2022
Method of publishing: Limited access
https://doi.org/10.1111/febs.16663

In this issue, Ballin et al. report on their analysis of the substrate repertoire of SPPL2a and b intramembrane proteases. Based on the previous studies of their closest homologues, SPPL2c, SPPL3 and SPP, the authors hypothesized that SPPL2a/b proteases may cleave a subset of SNARE proteins. Indeed, four R-SNARE proteins, VAMP1, 2, 3 and 4, were cleaved by SPPL2a/b, both in overexpression assays and at endogenous levels. These findings have been validated by analysis of SPPL2a/b double knock-out mice tissues, which implicates these proteases in the regulation of SNARE protein turnover in vivo. The study of Ballin et al. also provides material for future studies of factors determining substrate specificity of SPPLs, as they cleave different subsets of the tail-anchored SNARE proteins.
Permanent Link: https://hdl.handle.net/11104/0342661