English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Signal Peptide Peptidase-Like 2c (SPPL2c) impairs vesicular transport and cleavage of SNARE proteins

MPS-Authors
/persons/resource/persons77771

von Blume,  Julia
von Blume, Julia / Molecular Basis of Protein Trafficking, Max Planck Institute of Biochemistry, Max Planck Society;

Locator
There are no locators available
Fulltext (public)

embr.201846451.pdf
(Publisher version), 9MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Papadopoulou, A. A., Mueller, S. A., Mentrup, T., Shmueli, M. D., Niemeyer, J., Haug-Kroeper, M., et al. (2019). Signal Peptide Peptidase-Like 2c (SPPL2c) impairs vesicular transport and cleavage of SNARE proteins. EMBO Reports, 20(3): e46451. doi:10.15252/embr.201846451.


Cite as: http://hdl.handle.net/21.11116/0000-0003-E9ED-C
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.