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Papadopoulou, A.A.* ; Müller, S.A.* ; Mentrup, T.* ; Shmueli, M.D.* ; Niemeyer, J.* ; Haug-Kröper, M.* ; von Blume, J.* ; Mayerhofer, A.* ; Feederle, R. ; Schröder, B.* ; Lichtenthaler, S.F.* ; Fluhrer, R.*

Signal peptide peptidase-like 2c impairs vesicular transport and cleaves SNARE proteins.

EMBO Rep. 20:e46451 (2019)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Snare ; Spp/sppl-family ; Glycosyltransferases ; Intramembrane Proteases ; Spermatogenesis; Requirements; Extraction; Expression; Proteases; Reveals; Binding; Er
Language english
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Journal EMBO Reports
Quellenangaben Volume: 20, Issue: 3, Pages: , Article Number: e46451 Supplement: ,
Publisher EMBO Press
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Reviewing status Peer reviewed
Institute(s) CF Monoclonal Antibodies (CF-MAB)
Institute of Diabetes and Obesity (IDO)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502210-001
DOI 10.15252/embr.201846451
WOS ID WOS:000462657200004
Scopus ID 85061268800
PubMed ID 32048434
PubMed ID 30733281
Erfassungsdatum 2019-03-11
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