The intramembrane proteases SPPL2a and SPPL2b regulate the homeostasis of selected SNARE proteins.
SNARE protein
intramembrane proteolysis
membrane trafficking
protein degradation
signal peptide peptidase-like proteases
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
28
06
2022
received:
15
03
2022
accepted:
30
08
2022
medline:
4
5
2023
pubmed:
2
9
2022
entrez:
1
9
2022
Statut:
ppublish
Résumé
Signal peptide peptidase (SPP) and SPP-like (SPPL) aspartyl intramembrane proteases are known to contribute to sequential processing of type II-oriented membrane proteins referred to as regulated intramembrane proteolysis. The ER-resident family members SPP and SPPL2c were shown to also cleave tail-anchored proteins, including selected SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins facilitating membrane fusion events. Here, we analysed whether the related SPPL2a and SPPL2b proteases, which localise to the endocytic or late secretory pathway, are also able to process SNARE proteins. Therefore, we screened 18 SNARE proteins for cleavage by SPPL2a and SPPL2b based on cellular co-expression assays, of which the proteins VAMP1, VAMP2, VAMP3 and VAMP4 were processed by SPPL2a/b demonstrating the capability of these two proteases to proteolyse tail-anchored proteins. Cleavage of the four SNARE proteins was scrutinised at the endogenous level upon SPPL2a/b inhibition in different cell lines as well as by analysing VAMP1-4 levels in tissues and primary cells of SPPL2a/b double-deficient (dKO) mice. Loss of SPPL2a/b activity resulted in an accumulation of VAMP1-4 in a cell type- and tissue-dependent manner, identifying these proteins as SPPL2a/b substrates validated in vivo. Therefore, we propose that SPPL2a/b control cellular levels of VAMP1-4 by initiating the degradation of these proteins, which might impact cellular trafficking.
Substances chimiques
Aspartic Acid Endopeptidases
EC 3.4.23.-
Membrane Proteins
0
Peptide Hydrolases
EC 3.4.-
SPPL2a protein, mouse
EC 3.4.23.-
Vesicle-Associated Membrane Protein 1
0
SPPL2b protein, mouse
EC 3.4.23.-
Banques de données
RefSeq
['NM_016810.4', 'NM_016801.4', 'NM_024414.2', 'NM_007941.3', 'NM_152220.2', 'NM_001286543.2', 'NM_009294.3', 'NM_021433.3', 'NM_001358563.1', 'NM_133887.4', 'NM_172675.4', 'NM_009496.3', 'NM_001080557.1', 'NM_009497.3', 'NM_009498.4', 'NM_001356526.1', 'NM_001347125.1', 'NM_001080742.2', 'NM_016794.3', 'NM_016862.4', 'NM_016800.3']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2320-2337Informations de copyright
© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Références
Mentrup T, Schröder B. Signal peptide peptidase-like 2 proteases: regulatory switches or proteasome of the membrane? Biochim Biophys Acta Mol Cell Res. 2022;1869:119163.
Mentrup T, Cabrera-Cabrera F, Fluhrer R, Schröder B. Physiological functions of SPP/SPPL intramembrane proteases. Cell Mol Life Sci. 2020;77:2959-79.
Voss M, Kunzel U, Higel F, Kuhn PH, Colombo A, Fukumori A, et al. Shedding of glycan-modifying enzymes by signal peptide peptidase-like 3 (SPPL3) regulates cellular N-glycosylation. EMBO J. 2014;33:2890-905.
Kuhn PH, Voss M, Haug-Kroper M, Schröder B, Schepers U, Brase S, et al. Secretome analysis identifies novel signal peptide peptidase-like 3 (Sppl3) substrates and reveals a role of Sppl3 in multiple Golgi glycosylation pathways. Mol Cell Proteomics. 2015;14:1584-98.
Voss M, Fukumori A, Kuhn PH, Kunzel U, Klier B, Grammer G, et al. Foamy virus envelope protein is a substrate for signal peptide peptidase-like 3 (SPPL3). J Biol Chem. 2012;287:43401-9.
Martin L, Fluhrer R, Haass C. Substrate requirements for SPPL2b-dependent regulated intramembrane proteolysis. J Biol Chem. 2009;284:5662-70.
Chen CY, Malchus NS, Hehn B, Stelzer W, Avci D, Langosch D, et al. Signal peptide peptidase functions in ERAD to cleave the unfolded protein response regulator XBP1u. EMBO J. 2014;33:2492-506.
Spitz C, Schlosser C, Guschtschin-Schmidt N, Stelzer W, Menig S, Gotz A, et al. Non-canonical shedding of TNFalpha by SPPL2a is determined by the conformational flexibility of its transmembrane helix. iScience. 2020;23:101775.
Lichtenthaler SF, Lemberg MK, Fluhrer R. Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments. EMBO J. 2018;37:e99456.
Boname JM, Bloor S, Wandel MP, Nathan JA, Antrobus R, Dingwell KS, et al. Cleavage by signal peptide peptidase is required for the degradation of selected tail-anchored proteins. J Cell Biol. 2014;205:847-62.
Hsu FF, Yeh CT, Sun YJ, Chiang MT, Lan WM, Li FA, et al. Signal peptide peptidase-mediated nuclear localization of heme oxygenase-1 promotes cancer cell proliferation and invasion independent of its enzymatic activity. Oncogene. 2015;34:2360-70.
Avci D, Malchus NS, Heidasch R, Lorenz H, Richter K, Nessling M, et al. The intramembrane protease SPP impacts morphology of the endoplasmic reticulum by triggering degradation of morphogenic proteins. J Biol Chem. 2019;294:2786-800.
Rabu C, Schmid V, Schwappach B, High S. Biogenesis of tail-anchored proteins: the beginning for the end? J Cell Sci. 2009;122:3605-12.
Schuldiner M, Metz J, Schmid V, Denic V, Rakwalska M, Schmitt HD, et al. The GET complex mediates insertion of tail-anchored proteins into the ER membrane. Cell. 2008;134:634-45.
Farkas A, Bohnsack KE. Capture and delivery of tail-anchored proteins to the endoplasmic reticulum. J Cell Biol. 2021;220:e202105004.
Niemeyer J, Mentrup T, Heidasch R, Muller SA, Biswas U, Meyer R, et al. The intramembrane protease SPPL2c promotes male germ cell development by cleaving phospholamban. EMBO Rep. 2019;20:e46449.
Papadopoulou AA, Muller SA, Mentrup T, Shmueli MD, Niemeyer J, Haug-Kroper M, et al. Signal peptide peptidase-like 2c (SPPL2c) impairs vesicular transport and cleavage of SNARE proteins. EMBO Rep. 2019;20:e46451.
Kalbfleisch T, Cambon A, Wattenberg BW. A bioinformatics approach to identifying tail-anchored proteins in the human genome. Traffic. 2007;8:1687-94.
Wang T, Li L, Hong W. SNARE proteins in membrane trafficking. Traffic. 2017;18:767-75.
Sudhof TC. Neurotransmitter release: the last millisecond in the life of a synaptic vesicle. Neuron. 2013;80:675-90.
Dingjan I, Linders PTA, Verboogen DRJ, Revelo NH, Ter Beest M, van den Bogaart G. Endosomal and Phagosomal SNAREs. Physiol Rev. 2018;98:1465-92.
Bombardier JP, Munson M. Three steps forward, two steps back: mechanistic insights into the assembly and disassembly of the SNARE complex. Curr Opin Chem Biol. 2015;29:66-71.
Sankaranarayanan S, Ryan TA. Real-time measurements of vesicle-SNARE recycling in synapses of the central nervous system. Nat Cell Biol. 2000;2:197-204.
Rutledge TW, Whiteheart SW. SNAP-23 is a target for calpain cleavage in activated platelets. J Biol Chem. 2002;277:37009-15.
Zimmerman UJ, Malek SK, Liu L, Li HL. Proteolysis of synaptobrevin, syntaxin, and SNAP-25 in alveolar epithelial type II cells. IUBMB Life. 1999;48:453-8.
Tran TH, Zeng Q, Hong W. VAMP4 cycles from the cell surface to the trans-Golgi network via sorting and recycling endosomes. J Cell Sci. 2007;120:1028-41.
Mentrup T, Loock AC, Fluhrer R, Schröder B. Signal peptide peptidase and SPP-like proteases - possible therapeutic targets? Biochim Biophys Acta. 2017;1864:2169-82.
Schneppenheim J, Hüttl S, Mentrup T, Lüllmann-Rauch R, Rothaug M, Engelke M, et al. The intramembrane proteases signal peptide peptidase-like 2a and 2b have distinct functions in vivo. Mol Cell Biol. 2014;34:1398-411.
Herculano-Houzel S. The glia/neuron ratio: how it varies uniformly across brain structures and species and what that means for brain physiology and evolution. Glia. 2014;62:1377-91.
Laurent SA, Hoffmann FS, Kuhn PH, Cheng Q, Chu Y, Schmidt-Supprian M, et al. Gamma-secretase directly sheds the survival receptor BCMA from plasma cells. Nat Commun. 2015;6:7333.
Langosch D, Scharnagl C, Steiner H, Lemberg MK. Understanding intramembrane proteolysis: from protein dynamics to reaction kinetics. Trends Biochem Sci. 2015;40:318-27.
Ropert N, Jalil A, Li D. Expression and cellular function of vSNARE proteins in brain astrocytes. Neuroscience. 2016;323:76-83.
Schwarz Y, Zhao N, Kirchhoff F, Bruns D. Astrocytes control synaptic strength by two distinct v-SNARE-dependent release pathways. Nat Neurosci. 2017;20:1529-39.
Bezzi P, Gundersen V, Galbete JL, Seifert G, Steinhauser C, Pilati E, et al. Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat Neurosci. 2004;7:613-20.
Parpura V, Fang Y, Basarsky T, Jahn R, Haydon PG. Expression of synaptobrevin II, cellubrevin and syntaxin but not SNAP-25 in cultured astrocytes. FEBS Lett. 1995;377:489-92.
Madison DL, Krueger WH, Cheng D, Trapp BD, Pfeiffer SE. SNARE complex proteins, including the cognate pair VAMP-2 and syntaxin-4, are expressed in cultured oligodendrocytes. J Neurochem. 1999;72:988-98.
Feldmann A, Winterstein C, White R, Trotter J, Kramer-Albers EM. Comprehensive analysis of expression, subcellular localization, and cognate pairing of SNARE proteins in oligodendrocytes. J Neurosci Res. 2009;87:1760-72.
Feldmann A, Amphornrat J, Schonherr M, Winterstein C, Mobius W, Ruhwedel T, et al. Transport of the major myelin proteolipid protein is directed by VAMP3 and VAMP7. J Neurosci. 2011;31:5659-72.
Stow JL, Manderson AP, Murray RZ. SNAREing immunity: the role of SNAREs in the immune system. Nat Rev Immunol. 2006;6:919-29.
Bakr M, Jullie D, Krapivkina J, Paget-Blanc V, Bouit L, Petersen JD, et al. The vSNAREs VAMP2 and VAMP4 control recycling and intracellular sorting of post-synaptic receptors in neuronal dendrites. Cell Rep. 2021;36:109678.
Ye J. Transcription factors activated through RIP (regulated intramembrane proteolysis) and RAT (regulated alternative translocation). J Biol Chem. 2020;295:10271-80.
Papadopoulou AA, Fluhrer R. Signaling functions of intramembrane aspartyl-proteases. Front Cardiovasc Med. 2020;7:591787.
Scales SJ, Chen YA, Yoo BY, Patel SM, Doung YC, Scheller RH. SNAREs contribute to the specificity of membrane fusion. Neuron. 2000;26:457-64.
Hua Y, Scheller RH. Three SNARE complexes cooperate to mediate membrane fusion. Proc Natl Acad Sci USA. 2001;98:8065-70.
Chin LS, Vavalle JP, Li L. Staring, a novel E3 ubiquitin-protein ligase that targets syntaxin 1 for degradation. J Biol Chem. 2002;277:35071-9.
Sheehan P, Zhu M, Beskow A, Vollmer C, Waites CL. Activity-dependent degradation of synaptic vesicle proteins requires Rab35 and the ESCRT pathway. J Neurosci. 2016;36:8668-86.
Ivanova D, Dobson KL, Gajbhiye A, Davenport EC, Hacker D, Ultanir SK, et al. Control of synaptic vesicle release probability via VAMP4 targeting to endolysosomes. Sci Adv. 2021;7:eabf3873.
Babst M, Odorizzi G. The balance of protein expression and degradation: an ESCRTs point of view. Curr Opin Cell Biol. 2013;25:489-94.
Yamazaki Y, Schonherr C, Varshney GK, Dogru M, Hallberg B, Palmer RH. Goliath family E3 ligases regulate the recycling endosome pathway via VAMP3 ubiquitylation. EMBO J. 2013;32:524-37.
Banks GT, Guillaumin MCC, Heise I, Lau P, Yin M, Bourbia N, et al. Forward genetics identifies a novel sleep mutant with sleep state inertia and REM sleep deficits. Sci Adv. 2020;6:eabb3567.
Rossetto O, Gorza L, Schiavo G, Schiavo N, Scheller RH, Montecucco C. VAMP/synaptobrevin isoforms 1 and 2 are widely and differentially expressed in nonneuronal tissues. J Cell Biol. 1996;132:167-79.
Regazzi R, Wollheim CB, Lang J, Theler JM, Rossetto O, Montecucco C, et al. VAMP-2 and cellubrevin are expressed in pancreatic beta-cells and are essential for ca(2+)-but not for GTP gamma S-induced insulin secretion. EMBO J. 1995;14:2723-30.
Sadler JB, Bryant NJ, Gould GW. Characterization of VAMP isoforms in 3T3-L1 adipocytes: implications for GLUT4 trafficking. Mol Biol Cell. 2015;26:530-6.
Tajika Y, Takahashi M, Khairani AF, Ueno H, Murakami T, Yorifuji H. Vesicular transport system in myotubes: ultrastructural study and signposting with vesicle-associated membrane proteins. Histochem Cell Biol. 2014;141:441-54.
De Blas GA, Roggero CM, Tomes CN, Mayorga LS. Dynamics of SNARE assembly and disassembly during sperm acrosomal exocytosis. PLoS Biol. 2005;3:e323.
Guo X, Shen J, Xia Z, Zhang R, Zhang P, Zhao C, et al. Proteomic analysis of proteins involved in spermiogenesis in mouse. J Proteome Res. 2010;9:1246-56.
Behnke J, Schneppenheim J, Koch-Nolte F, Haag F, Saftig P, Schröder B. Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail. FEBS Lett. 2011;585:2951-7.
Schneppenheim J, Dressel R, Hüttl S, Lüllmann-Rauch R, Engelke M, Dittmann K, et al. The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain. J Exp Med. 2013;210:41-58.
Gradtke AC, Mentrup T, Lehmann CHK, Cabrera-Cabrera F, Desel C, Okakpu D, et al. Deficiency of the intramembrane protease SPPL2a alters antimycobacterial cytokine responses of dendritic cells. J Immunol. 2021;206:164-80.
Mentrup T, Stumpff-Niggemann AY, Leinung N, Schlosser C, Schubert K, Wehner R, et al. Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis. Nat Commun. 2022;13:1880.
Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680-5.
Schröder B, Wrocklage C, Hasilik A, Saftig P. Molecular characterisation of 'transmembrane protein 192′ (TMEM192), a novel protein of the lysosomal membrane. Biol Chem. 2010;391:695-704.
Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671-675.