Signal peptide peptidase-like 2c impairs vesicular transport and cleaves SNARE proteins.
Acrosome
/ metabolism
Animals
Aspartic Acid Endopeptidases
/ metabolism
Biocatalysis
Down-Regulation
Glycomics
Glycoproteins
/ metabolism
Glycosyltransferases
/ metabolism
Golgi Apparatus
/ metabolism
HEK293 Cells
Humans
Male
Membrane Proteins
/ metabolism
Mice, Inbred C57BL
Models, Biological
Protein Transport
Proteolysis
SNARE Proteins
/ metabolism
Spermatids
/ metabolism
Subcellular Fractions
/ metabolism
Substrate Specificity
SNARE
SPP/SPPL‐family
glycosyltransferases
intramembrane proteases
spermatogenesis
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
18
05
2018
revised:
07
12
2018
accepted:
21
12
2018
pubmed:
9
2
2019
medline:
28
4
2020
entrez:
9
2
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30733281
pii: embr.201846451
doi: 10.15252/embr.201846451
pmc: PMC6399617
pii:
doi:
Substances chimiques
Glycoproteins
0
Membrane Proteins
0
SNARE Proteins
0
Glycosyltransferases
EC 2.4.-
Aspartic Acid Endopeptidases
EC 3.4.23.-
SPPL2C protein, human
EC 3.4.23.-
Sppl2c protein, mouse
EC 3.4.23.-
signal peptide peptidase
EC 3.4.23.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2019 The Authors.
Références
Biochim Biophys Acta Mol Cell Res. 2017 Nov;1864(11 Pt B):2169-2182
pubmed: 28624439
Sci Rep. 2016 Feb 01;6:20249
pubmed: 26832966
Science. 1998 Jan 30;279(5351):696-700
pubmed: 9445473
Biochim Biophys Acta. 2013 Dec;1828(12):2828-39
pubmed: 24099004
Arch Biochem Biophys. 2000 Jul 15;379(2):173-82
pubmed: 10898932
EMBO Rep. 2019 Mar;20(3):
pubmed: 30733280
J Cell Biol. 2016 May 9;213(3):305-14
pubmed: 27138253
J Biol Chem. 2012 Feb 10;287(7):5156-63
pubmed: 22194595
Genome Biol. 2001;2(11):REVIEWS3012
pubmed: 11737951
J Biol Chem. 2000 Oct 6;275(40):30951-6
pubmed: 10921927
Nucleic Acids Res. 2016 Jan 4;44(D1):D447-56
pubmed: 26527722
J Biol Chem. 2012 Dec 21;287(52):43401-9
pubmed: 23132852
Nat Rev Mol Cell Biol. 2006 Sep;7(9):631-43
pubmed: 16912714
Mol Cell Proteomics. 2015 Jun;14(6):1584-98
pubmed: 25827571
J Biol Chem. 2004 Dec 3;279(49):50790-8
pubmed: 15385547
Oncogene. 2015 Apr 30;34(18):2360-70
pubmed: 24931165
J Cell Biol. 2014 Jun 23;205(6):847-62
pubmed: 24958774
FEBS Lett. 2011 Oct 3;585(19):2951-7
pubmed: 21896273
Eur J Cell Biol. 2017 Aug;96(5):372-382
pubmed: 28366434
Mol Hum Reprod. 1997 Jul;3(7):599-637
pubmed: 9268137
J Biol Chem. 2009 Feb 27;284(9):5662-70
pubmed: 19114711
J Cell Biol. 2001 Nov 12;155(4):557-70
pubmed: 11706049
Methods Mol Biol. 2013;927:299-307
pubmed: 22992924
Sci Rep. 2016 Nov 16;6:37128
pubmed: 27849015
Mol Cell. 2002 Oct;10(4):735-44
pubmed: 12419218
J Exp Med. 2013 Jan 14;210(1):41-58
pubmed: 23267015
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
Traffic. 2017 Dec;18(12):767-775
pubmed: 28857378
Proc Natl Acad Sci U S A. 1988 Jun;85(12):4538-42
pubmed: 3380805
Semin Cell Dev Biol. 2009 Apr;20(2):225-30
pubmed: 19429495
Cell. 2004 Jan 23;116(2):153-66
pubmed: 14744428
Biochim Biophys Acta. 2006 Mar-Apr;1759(3-4):159-65
pubmed: 16730383
Science. 2011 Sep 23;333(6050):1761-4
pubmed: 21852454
Sci Data. 2017 Aug 29;4:170112
pubmed: 28850106
Annu Rev Cell Dev Biol. 2004;20:87-123
pubmed: 15473836
Mol Cell Proteomics. 2014 Sep;13(9):2513-26
pubmed: 24942700
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
pubmed: 11309499
Biol Chem. 2010 Jun;391(6):695-704
pubmed: 20370317
Nat Methods. 2009 May;6(5):359-62
pubmed: 19377485
Mol Reprod Dev. 2015 Sep;82(9):635-50
pubmed: 26061344
Nat Cell Biol. 2000 Nov;2(11):848-51
pubmed: 11056541
J Cell Biol. 2016 Dec 19;215(6):769-778
pubmed: 27903609
Biosci Rep. 2012 Aug;32(4):383-91
pubmed: 22489884
EMBO J. 2014 Dec 17;33(24):2890-905
pubmed: 25354954
Mol Cell. 2000 Sep;6(3):625-36
pubmed: 11030342
Spermatogenesis. 2011 Apr;1(2):95-98
pubmed: 22319656
J Biol Chem. 2003 May 9;278(19):16528-33
pubmed: 12621027
Anal Chem. 2003 Feb 1;75(3):663-70
pubmed: 12585499
J Biol Chem. 2016 Jan 1;291(1):318-33
pubmed: 26574544