000151555 001__ 151555 000151555 005__ 20250416100053.0 000151555 0247_ $$2pmid$$apmid:32052089 000151555 0247_ $$2doi$$a10.1007/s00018-020-03470-6 000151555 0247_ $$2ISSN$$a0014-4754 000151555 0247_ $$2ISSN$$a1420-682X 000151555 0247_ $$2ISSN$$a1420-9071 000151555 0247_ $$2pmc$$apmc:PMC7366577 000151555 037__ $$aDZNE-2020-01139 000151555 041__ $$aEnglish 000151555 082__ $$a610 000151555 1001_ $$aMentrup, Torben$$b0 000151555 245__ $$aPhysiological functions of SPP/SPPL intramembrane proteases 000151555 260__ $$aCham (ZG)$$bSpringer International Publishing AG$$c2020 000151555 264_1 $$2Crossref$$3online$$bSpringer Science and Business Media LLC$$c2020-02-12 000151555 264_1 $$2Crossref$$3print$$bSpringer Science and Business Media LLC$$c2020-08-01 000151555 3367_ $$2DRIVER$$aarticle 000151555 3367_ $$2DataCite$$aOutput Types/Journal article 000151555 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1744708713_29013 000151555 3367_ $$2BibTeX$$aARTICLE 000151555 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000151555 3367_ $$00$$2EndNote$$aJournal Article 000151555 520__ $$aIntramembrane proteolysis describes the cleavage of substrate proteins within their hydrophobic transmembrane segments. Several families of intramembrane proteases have been identified including the aspartyl proteases Signal peptide peptidase (SPP) and its homologues, the SPP-like (SPPL) proteases SPPL2a, SPPL2b, SPPL2c and SPPL3. As presenilin homologues, they employ a similar catalytic mechanism as the well-studied γ-secretase. However, SPP/SPPL proteases cleave transmembrane proteins with a type II topology. The characterisation of SPP/SPPL-deficient mouse models has highlighted a still growing spectrum of biological functions and also promoted the substrate discovery of these proteases. In this review, we will summarise the current hypotheses how phenotypes of these mouse models are linked to the molecular function of the enzymes. At the cellular level, SPP/SPPL-mediated cleavage events rather provide specific regulatory switches than unspecific bulk proteolysis. By this means, a plethora of different cell biological pathways is influenced including signal transduction, membrane trafficking and protein glycosylation. 000151555 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0 000151555 542__ $$2Crossref$$i2020-02-12$$uhttps://creativecommons.org/licenses/by/4.0 000151555 588__ $$aDataset connected to CrossRef 000151555 650_2 $$2MeSH$$aAmyloid Precursor Protein Secretases: metabolism 000151555 650_2 $$2MeSH$$aAnimals 000151555 650_2 $$2MeSH$$aAspartic Acid Endopeptidases: chemistry 000151555 650_2 $$2MeSH$$aAspartic Acid Endopeptidases: metabolism 000151555 650_2 $$2MeSH$$aHumans 000151555 650_2 $$2MeSH$$aMembrane Proteins: metabolism 000151555 650_2 $$2MeSH$$aProtein Transport 000151555 650_2 $$2MeSH$$aProteolysis 000151555 650_2 $$2MeSH$$aSignal Transduction 000151555 650_2 $$2MeSH$$aSubstrate Specificity 000151555 7001_ $$aCabrera-Cabrera, Florencia$$b1 000151555 7001_ $$0P:(DE-2719)2000007$$aFluhrer, Regina$$b2$$udzne 000151555 7001_ $$00000-0003-0774-6270$$aSchröder, Bernd$$b3$$eCorresponding author 000151555 77318 $$2Crossref$$3journal-article$$a10.1007/s00018-020-03470-6$$b : Springer Science and Business Media LLC, 2020-02-12$$n15$$p2959-2979$$tCellular and Molecular Life Sciences$$v77$$x1420-682X$$y2020 000151555 773__ $$0PERI:(DE-600)1458497-9$$a10.1007/s00018-020-03470-6$$gVol. 77, no. 15, p. 2959 - 2979$$n15$$p2959-2979$$tCellular and molecular life sciences$$v77$$x1420-682X$$y2020 000151555 8564_ $$uhttps://link.springer.com/article/10.1007/s00018-020-03470-6 000151555 8564_ $$uhttps://pub.dzne.de/record/151555/files/DZNE-2020-01139.pdf$$yOpenAccess 000151555 8564_ $$uhttps://pub.dzne.de/record/151555/files/DZNE-2020-01139.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000151555 909CO $$ooai:pub.dzne.de:151555$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery 000151555 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2000007$$aDeutsches Zentrum für 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--$$a10.1016/j.tibs.2018.06.009$$o10.1016/j.tibs.2018.06.009 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1083/jcb.201312009$$o10.1083/jcb.201312009 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/onc.2014.166$$o10.1038/onc.2014.166 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.RA118.005642$$o10.1074/jbc.RA118.005642 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrm1406$$o10.1038/nrm1406 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.M807485200$$o10.1074/jbc.M807485200 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.M111.328104$$o10.1074/jbc.M111.328104 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.M109.028001$$o10.1074/jbc.M109.028001 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1084/jem.20121069$$o10.1084/jem.20121069 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1152/physrev.00005.2017$$o10.1152/physrev.00005.2017 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/onc.2016.341$$o10.1038/onc.2016.341 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/tra.12287$$o10.1111/tra.12287 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1073/pnas.1612195114$$o10.1073/pnas.1612195114 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.15252/embr.201745603$$o10.15252/embr.201745603 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.M607954200$$o10.1074/jbc.M607954200 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1128/MCB.00038-14$$o10.1128/MCB.00038-14 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1084/jem.20121072$$o10.1084/jem.20121072 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1084/jem.20121076$$o10.1084/jem.20121076 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.bbrc.2014.07.051$$o10.1016/j.bbrc.2014.07.051 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/s41590-018-0178-z$$o10.1038/s41590-018-0178-z 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.4049/jimmunol.1403171$$o10.4049/jimmunol.1403171 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00018-012-1194-z$$o10.1007/s00018-012-1194-z 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrm1155$$o10.1038/nrm1155 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1128/MCB.01124-14$$o10.1128/MCB.01124-14 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrm1151$$o10.1038/nrm1151 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1096/fj.03-1058fje$$o10.1096/fj.03-1058fje 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.cub.2018.01.005$$o10.1016/j.cub.2018.01.005 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.4049/jimmunol.1601533$$o10.4049/jimmunol.1601533 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1146/annurev.bi.54.070185.003215$$o10.1146/annurev.bi.54.070185.003215 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s000180050146$$o10.1007/s000180050146 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrm3383$$o10.1038/nrm3383 000151555 999C5 $$2Crossref$$oJC Paulson 1989$$y1989 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.cell.2006.08.019$$o10.1016/j.cell.2006.08.019 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/s0304-4165(99)00167-1$$o10.1016/s0304-4165(99)00167-1 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/(SICI)1521-1878(199905)21:5%3c412::AID-BIES8%3e3.0.CO;2-5$$o10.1002/(SICI)1521-1878(199905)21:5%3c412::AID-BIES8%3e3.0.CO;2-5 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/35055582$$o10.1038/35055582 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.4049/jimmunol.1501970$$o10.4049/jimmunol.1501970 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/imcb.12210$$o10.1111/imcb.12210 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/CIRCRESAHA.114.302937$$o10.1161/CIRCRESAHA.114.302937 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/CIRCRESAHA.115.307611$$o10.1161/CIRCRESAHA.115.307611 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1042/bj20071196$$o10.1042/bj20071196 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/eurheartj/eht532$$o10.1093/eurheartj/eht532 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.4161/spmg.1.2.16820$$o10.4161/spmg.1.2.16820 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/molehr/gam012$$o10.1093/molehr/gam012 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1242/jcs.02297$$o10.1242/jcs.02297 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1152/physrev.00028.2010$$o10.1152/physrev.00028.2010 000151555 999C5 $$2Crossref$$9-- missing cx lookup 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missing cx lookup --$$a10.1073/pnas.1603364113$$o10.1073/pnas.1603364113 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1371/journal.pone.0085360$$o10.1371/journal.pone.0085360 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.exer.2014.04.004$$o10.1016/j.exer.2014.04.004 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1128/JVI.01309-19$$o10.1128/JVI.01309-19 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/jbmr.1895$$o10.1002/jbmr.1895 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1177/2472555217719834$$o10.1177/2472555217719834 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1021/acs.jmedchem.7b01371$$o10.1021/acs.jmedchem.7b01371 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1021/acsmedchemlett.9b00044$$o10.1021/acsmedchemlett.9b00044 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.bbamem.2013.06.005$$o10.1016/j.bbamem.2013.06.005 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.15252/emmm.201607265$$o10.15252/emmm.201607265 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1371/journal.pone.0128619$$o10.1371/journal.pone.0128619 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1600-0854.2012.01402.x$$o10.1111/j.1600-0854.2012.01402.x 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1056/NEJMoa1210951$$o10.1056/NEJMoa1210951 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.cell.2014.10.016$$o10.1016/j.cell.2014.10.016 000151555 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1371/journal.pone.0214968$$o10.1371/journal.pone.0214968