Journal Article

DZNE-2020-06927

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Signal Peptide Peptidase-Like 2c (SPPL2c) impairs vesicular transport and cleaves SNARE proteins.

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

2019
Wiley Hoboken, NJ [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.15252/embr.201846451

Abstract: 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.

Note: Title corrected according to Corrigendum: EMBO rep (2019) 20: e48133 https://doi.org/10.15252/embr.201948133

---

Contributing Institute(s):

1. Molecular Neurodegeneration (AG Haass)
2. Neuroproteomics (AG Lichtenthaler)
3. Antibody Production (AG Feederle)
4. Signal Peptide Peptidases as Models for γ-Secretase (AG Fluhrer)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2019

---

Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection

---