TY  - JOUR
AU  - Papadopoulou, Alkmini A
AU  - Müller, Stephan A
AU  - Mentrup, Torben
AU  - Shmueli, Merav D
AU  - Niemeyer, Johannes
AU  - Haug-Kröper, Martina
AU  - von Blume, Julia
AU  - Mayerhofer, Artur
AU  - Feederle, Regina
AU  - Schröder, Bernd
AU  - Lichtenthaler, Stefan F
AU  - Fluhrer, Regina
TI  - Signal Peptide Peptidase-Like 2c (SPPL2c) impairs vesicular transport and cleaves SNARE proteins.
JO  - EMBO reports
VL  - 20
IS  - 3
SN  - 1469-221X
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DZNE-2020-06927
SP  - e46451
PY  - 2019
N1  - Title corrected according to Corrigendum: EMBO rep (2019) 20: e48133 https://doi.org/10.15252/embr.201948133
AB  - Members of the GxGD-type intramembrane aspartyl proteases have emerged as key players not only in fundamental cellular processes such as B-cell development or protein glycosylation, but also in development of pathologies, such as Alzheimer's disease or hepatitis virus infections. However, one member of this protease family, signal peptide peptidase-like 2c (SPPL2c), remains orphan and its capability of proteolysis as well as its physiological function is still enigmatic. Here, we demonstrate that SPPL2c is catalytically active and identify a variety of SPPL2c candidate substrates using proteomics. The majority of the SPPL2c candidate substrates cluster to the biological process of vesicular trafficking. Analysis of selected SNARE proteins reveals proteolytic processing by SPPL2c that impairs vesicular transport and causes retention of cargo proteins in the endoplasmic reticulum. As a consequence, the integrity of subcellular compartments, in particular the Golgi, is disturbed. Together with a strikingly high physiological SPPL2c expression in testis, our data suggest involvement of SPPL2c in acrosome formation during spermatogenesis.
LB  - PUB:(DE-HGF)16
C6  - pmid:30733281
C2  - pmc:PMC6399617
DO  - DOI:10.15252/embr.201846451
UR  - https://pub.dzne.de/record/140605
ER  -