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

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,...

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Bibliographic Details
Published in:The FEBS journal 2023-05, Vol.290 (9), p.2306-2310
Main Authors: Trávníčková, Květa, Stříšovský, Kvido
Format: Article
Language:English
Subjects:
Amyloid Precursor Protein Secretases - metabolism
Animal models
Animal tissues
Animals
Aspartic Acid Endopeptidases - metabolism
In vivo methods and tests
intramembrane protease
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Models, Animal
Protein turnover
Proteins
Proteolysis
signal peptide peptidase‐like
SNAP receptors
SNARE
Substrate specificity
Substrates
trafficking
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Summary: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. Comment on: https://doi.org/10.1111/febs.16610 In this issue, Ballin et al. report the identification of new substrates of SPPL2a and b intramembrane proteases. A subset of R‐SNARE proteins, VAMP1, 2, 3 and 4, were found to be cleaved by SPPL2a/b in overexpression assays and at endogenous levels in mouse tissues. These findings implicate SPPL2a/b in the regulation of SNARE protein turnover and possibly trafficking, and provide material for future studies of substrate specificity of SPPLs. Comment on: https://doi.org/10.1111/febs.16610
ISSN:1742-464X
1742-4658
DOI:10.1111/febs.16663