Signal peptide peptidase-like 2c (SPPL2c) is the only member of the GxGD type intramembrane-cleaving aspartyl proteases that so far has not been assigned any substrates and thus its capability of proteolysis and its physiological function remain enigmatic. Based on a surprisingly high expression of SPPL2c in elongated spermatids we applied proteomics on a cellular model system with ectopic expression of SPPL2c and identified a variety of candidate substrates. The majority of these candidate substrates clusters 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. This may be the trigger for the compartmental reorganization observed during spermatogenesis, which finally results in loss of the majority of endoplasmic reticulum, Golgi and parts of the cytosol in the mature sperm.
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Created: 8th Jul 2024 at 10:42
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Version 1 (earliest) Created 8th Jul 2024 at 10:42 by Rainer Malik
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Projects: SyNergy - published datasets
Institutions: DZNE
Projects: SyNergy - published datasets
Institutions: Klinikum der Universität München
Projects: SyNergy - published datasets
Institutions: DZNE
Public web page: Not specified
Organisms: Mus musculus, Rattus norvegicus, Homo sapiens, Macaca mulatta, Sus scrofa
Submitter: Rainer Malik
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Signal peptide peptidase-like 2c (SPPL2c) is the only member of the GxGD type intramembrane-cleaving aspartyl proteases that so far has not been assigned any substrates and thus its capability of proteolysis and its physiological function remain enigmatic. Based on a surprisingly high expression of SPPL2c in elongated spermatids we applied proteomics on a cellular model system with ectopic expression of SPPL2c and identified a variety of candidate substrates. The majority of these candidate ...
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Cells were harvested and centrifuged 400g for 10 min at 4°C. Cell pellets were resuspended in STE-Buffer (250mM sucrose, 5mM Tris pH 7, 1mM EGTA, PI mix 1:500) and lysed with a 27-gauge needle. Samples were centrifuged 10 min at 800g to remove nuclei, then 10 min at 15.000g to remove mitochondria and finally 1 hour 100.000g. The resulting pellets were washed twice with 100mM Na2CO3 and centrifuged 30 min at 100000g after each wash. Pellets from membrane preparations were dissolved in lysis buffer ...
Submitter: Rainer Malik
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Proteomics
Organisms: Homo sapiens
SOPs: No SOPs
Data files: Quantitative Proteomics of SPPL2c overexpressin...
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Abstract (Expand)
Authors: A. A. Papadopoulou, S. A. Muller, T. Mentrup, M. D. Shmueli, J. Niemeyer, M. Haug-Kroper, J. von Blume, A. Mayerhofer, R. Feederle, B. Schroder, S. F. Lichtenthaler, R. Fluhrer
Date Published: 9th Feb 2019
Publication Type: Journal
PubMed ID: 30733281
Citation: EMBO Rep. 2019 Mar;20(3):e46451. doi: 10.15252/embr.201846451. Epub 2019 Feb 7.