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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)
Publ. Version/Full Text Preprint DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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
Corresponding Author
Keywords Snare ; Spp/sppl-family ; Glycosyltransferases ; Intramembrane Proteases ; Spermatogenesis; Requirements; Extraction; Expression; Proteases; Reveals; Binding; Er
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
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CF Monoclonal Antibodies (CF-MAB)
Institute of Diabetes and Obesity (IDO)