{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T10:31:51Z","timestamp":1783765911850,"version":"3.55.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T00:00:00Z","timestamp":1729900800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T00:00:00Z","timestamp":1729900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002957","name":"Technische Universit\u00e4t Dresden","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002957","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell. Mol. Life Sci."],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Signal peptide peptidase-like 2c (SPPL2c) is a testis-specific aspartyl intramembrane protease that contributes to male gamete function both by catalytic and non-proteolytic mechanisms. Here, we provide an unbiased characterisation of the in vivo interactome of SPPL2c identifying the ER chaperone calnexin as novel binding partner of this enzyme. Recruitment of calnexin specifically required the N-glycosylation within the N-terminal protease-associated domain of SPPL2c. Importantly, mutation of the single glycosylation site of SPPL2c or loss of calnexin expression completely prevented SPPL2c-mediated intramembrane proteolysis of all tested substrates. By contrast and despite rather promiscuous binding of calnexin to other SPP\/SPPL proteases, expression of the chaperone was exclusively required for SPPL2c-mediated proteolysis. Despite some impact on the stability of SPPL2c most presumably due to assistance in folding of the luminal domain of the protease, calnexin appeared to be recruited rather constitutively to the protease thereby boosting its catalytic activity. In summary, we describe a novel, highly specific mode of intramembrane protease regulation, highlighting the need to systematically approach control mechanisms governing the proteolytic activity of other members of the aspartyl intramembrane protease family.<\/jats:p>","DOI":"10.1007\/s00018-024-05478-8","type":"journal-article","created":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T05:02:16Z","timestamp":1729918936000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Selective regulation of aspartyl intramembrane protease activity by calnexin"],"prefix":"10.1007","volume":"81","author":[{"given":"Whendy","family":"Contreras","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jody","family":"Groenendyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Gentzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal Y.","family":"Sch\u00f6nberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Buchholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Michalak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Schr\u00f6der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4570-8734","authenticated-orcid":false,"given":"Torben","family":"Mentrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,26]]},"reference":[{"issue":"12","key":"5478_CR1","doi-asserted-by":"publisher","first-page":"2828","DOI":"10.1016\/j.bbamem.2013.03.033","volume":"1828","author":"M Voss","year":"2013","unstructured":"Voss M, Schr\u00f6der B, Fluhrer R (2013) Mechanism, specificity, and physiology of signal peptide peptidase (SPP) and SPP-like proteases. Biochim Biophys Acta 1828(12):2828\u20132839. https:\/\/doi.org\/10.1016\/j.bbamem.2013.03.033","journal-title":"Biochim Biophys Acta"},{"issue":"11","key":"5478_CR2","doi-asserted-by":"publisher","first-page":"119345","DOI":"10.1016\/j.bbamcr.2022.119345","volume":"1869","author":"J Truberg","year":"2022","unstructured":"Truberg J, Hobohm L, Jochimsen A et al (2022) Endogenous tagging reveals a mid-golgi localization of the glycosyltransferase-cleaving intramembrane protease SPPL3. Biochimica et biophysica acta. Mol cell Res 1869(11):119345. https:\/\/doi.org\/10.1016\/j.bbamcr.2022.119345","journal-title":"Mol cell Res"},{"issue":"19","key":"5478_CR3","doi-asserted-by":"publisher","first-page":"2951","DOI":"10.1016\/j.febslet.2011.08.043","volume":"585","author":"J Behnke","year":"2011","unstructured":"Behnke J, Schneppenheim J, Koch-Nolte F et al (2011) Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes\/late endosomes by a tyrosine motif in its C-terminal tail. FEBS Lett 585(19):2951\u20132957. https:\/\/doi.org\/10.1016\/j.febslet.2011.08.043","journal-title":"FEBS Lett"},{"issue":"49","key":"5478_CR4","doi-asserted-by":"publisher","first-page":"50790","DOI":"10.1074\/jbc.M407898200","volume":"279","author":"E Friedmann","year":"2004","unstructured":"Friedmann E, Lemberg MK, Weihofen A et al (2004) Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins. J Biol Chem 279(49):50790\u201350798. https:\/\/doi.org\/10.1074\/jbc.M407898200","journal-title":"J Biol Chem"},{"key":"5478_CR5","doi-asserted-by":"publisher","unstructured":"Niemeyer J, Mentrup T, Heidasch R et al (2019) The intramembrane protease SPPL2c promotes male germ cell development by cleaving phospholamban. EMBO Rep 20(3). https:\/\/doi.org\/10.15252\/embr.201846449","DOI":"10.15252\/embr.201846449"},{"issue":"5576","key":"5478_CR6","doi-asserted-by":"publisher","first-page":"2215","DOI":"10.1126\/science.1070925","volume":"296","author":"A Weihofen","year":"2002","unstructured":"Weihofen A, Binns K, Lemberg MK et al (2002) Identification of signal peptide peptidase, a presenilin-type aspartic protease. Science 296(5576):2215\u20132218. https:\/\/doi.org\/10.1126\/science.1070925","journal-title":"Science"},{"issue":"18","key":"5478_CR7","doi-asserted-by":"publisher","first-page":"2410","DOI":"10.1038\/onc.2014.464","volume":"34","author":"FF Hsu","year":"2015","unstructured":"Hsu FF, Yeh CT, Sun YJ et al (2015) Signal peptide peptidase-mediated nuclear localization of heme oxygenase-1 promotes cancer cell proliferation and invasion independent of its enzymatic activity. Oncogene 34(18):2410\u20132411. https:\/\/doi.org\/10.1038\/onc.2014.464","journal-title":"Oncogene"},{"issue":"10","key":"5478_CR8","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1038\/s41388-018-0539-y","volume":"38","author":"FF Hsu","year":"2019","unstructured":"Hsu FF, Chou YT, Chiang MT et al (2019) Signal peptide peptidase promotes tumor progression via facilitating FKBP8 degradation. Oncogene 38(10):1688\u20131701. https:\/\/doi.org\/10.1038\/s41388-018-0539-y","journal-title":"Oncogene"},{"issue":"21","key":"5478_CR9","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.15252\/embj.201488208","volume":"33","author":"CY Chen","year":"2014","unstructured":"Chen CY, Malchus NS, Hehn B et al (2014) Signal peptide peptidase functions in ERAD to cleave the unfolded protein response regulator XBP1u. EMBO J 33(21):2492\u20132506. https:\/\/doi.org\/10.15252\/embj.201488208","journal-title":"EMBO J"},{"issue":"2","key":"5478_CR10","doi-asserted-by":"publisher","first-page":"105644","DOI":"10.1016\/j.jbc.2024.105644","volume":"300","author":"D Avci","year":"2024","unstructured":"Avci D, Heidasch R, Costa M et al (2024) Intramembrane protease SPP defines a cholesterol-regulated abundance control of the mevalonate pathway enzyme squalene synthase. J Biol Chem 300(2):105644. https:\/\/doi.org\/10.1016\/j.jbc.2024.105644","journal-title":"J Biol Chem"},{"issue":"15","key":"5478_CR11","doi-asserted-by":"publisher","first-page":"3980","DOI":"10.1093\/emboj\/cdf414","volume":"21","author":"J McLauchlan","year":"2002","unstructured":"McLauchlan J, Lemberg MK, Hope G et al (2002) Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets. EMBO J 21(15):3980\u20133988. https:\/\/doi.org\/10.1093\/emboj\/cdf414","journal-title":"EMBO J"},{"issue":"24","key":"5478_CR12","doi-asserted-by":"publisher","first-page":"2890","DOI":"10.15252\/embj.201488375","volume":"33","author":"M Voss","year":"2014","unstructured":"Voss M, K\u00fcnzel U, Higel F et al (2014) Shedding of glycan-modifying enzymes by signal peptide peptidase-like 3 (SPPL3) regulates cellular N-glycosylation. EMBO J 33(24):2890\u20132905. https:\/\/doi.org\/10.15252\/embj.201488375","journal-title":"EMBO J"},{"issue":"1","key":"5478_CR13","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1084\/jem.20121069","volume":"210","author":"J Schneppenheim","year":"2013","unstructured":"Schneppenheim J, Dressel R, Huttl S et al (2013) The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain. J Exp Med 210(1):41\u201358. https:\/\/doi.org\/10.1084\/jem.20121069","journal-title":"J Exp Med"},{"issue":"1","key":"5478_CR14","doi-asserted-by":"publisher","first-page":"164","DOI":"10.4049\/jimmunol.2000151","volume":"206","author":"A-C Gradtke","year":"2021","unstructured":"Gradtke A-C, Mentrup T, Lehmann CHK et al (2021) Deficiency of the intramembrane protease SPPL2a alters antimycobacterial cytokine responses of dendritic cells. J Immunol (Baltimore Md : 1950) 206(1):164\u2013180. https:\/\/doi.org\/10.4049\/jimmunol.2000151","journal-title":"J Immunol (Baltimore Md : 1950)"},{"issue":"1","key":"5478_CR15","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1038\/s41467-022-29474-3","volume":"13","author":"T Mentrup","year":"2022","unstructured":"Mentrup T, Stumpff-Niggemann AY, Leinung N et al (2022) Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis. Nat Commun 13(1):1880. https:\/\/doi.org\/10.1038\/s41467-022-29474-3","journal-title":"Nat Commun"},{"issue":"4","key":"5478_CR16","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1084\/jem.20171438","volume":"216","author":"T Mentrup","year":"2019","unstructured":"Mentrup T, Theodorou K, Cabrera-Cabrera F et al (2019) Atherogenic LOX-1 signaling is controlled by SPPL2-mediated intramembrane proteolysis. J Exp Med 216(4):807\u2013830. https:\/\/doi.org\/10.1084\/jem.20171438","journal-title":"J Exp Med"},{"key":"5478_CR17","doi-asserted-by":"publisher","unstructured":"Papadopoulou AA, Muller SA, Mentrup T et al (2019) Signal peptide peptidase-like 2c (SPPL2c) impairs vesicular transport and cleavage of SNARE proteins. EMBO Rep 20(3). https:\/\/doi.org\/10.15252\/embr.201846451","DOI":"10.15252\/embr.201846451"},{"issue":"4","key":"5478_CR18","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S0092-8674(00)80675-3","volume":"100","author":"MS Brown","year":"2000","unstructured":"Brown MS, Ye J, Rawson RB et al (2000) Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100(4):391\u2013398","journal-title":"Cell"},{"key":"5478_CR19","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16610","author":"M Ballin","year":"2022","unstructured":"Ballin M, Griep W, Patel M et al (2022) The intramembrane proteases SPPL2a and SPPL2b regulate the homeostasis of selected SNARE proteins. FEBS J. https:\/\/doi.org\/10.1111\/febs.16610","journal-title":"FEBS J"},{"issue":"6","key":"5478_CR20","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1083\/jcb.201312009","volume":"205","author":"JM Boname","year":"2014","unstructured":"Boname JM, Bloor S, Wandel MP et al (2014) Cleavage by signal peptide peptidase is required for the degradation of selected tail-anchored proteins. J Cell Biol 205(6):847\u2013862. https:\/\/doi.org\/10.1083\/jcb.201312009","journal-title":"J Cell Biol"},{"issue":"32","key":"5478_CR21","doi-asserted-by":"publisher","first-page":"eabo6049","DOI":"10.1126\/sciadv.abo6049","volume":"8","author":"W Contreras","year":"2022","unstructured":"Contreras W, Wieseh\u00f6fer C, Schreier D et al (2022) C11orf94\/Frey is a key regulator for male fertility by controlling Izumo1 complex assembly. Sci Adv 8(32):eabo6049. https:\/\/doi.org\/10.1126\/sciadv.abo6049","journal-title":"Sci Adv"},{"issue":"6","key":"5478_CR22","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1007\/s00018-023-04823-7","volume":"80","author":"W Contreras","year":"2023","unstructured":"Contreras W, Bazan JF, Mentrup T (2023) The transmembrane domain of Frey1 harbors a transplantable inhibitory motif for intramembrane proteases. Cell Mol Life Sci 80(6):170. https:\/\/doi.org\/10.1007\/s00018-023-04823-7","journal-title":"Cell Mol Life Sci"},{"issue":"1","key":"5478_CR23","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s43556-022-00092-1","volume":"3","author":"H Hao","year":"2022","unstructured":"Hao H, Shi B, Zhang J et al (2022) The vertebrate- and testis- specific transmembrane protein C11ORF94 plays a critical role in sperm-oocyte membrane binding. Mol Biomed 3(1):27. https:\/\/doi.org\/10.1186\/s43556-022-00092-1","journal-title":"Mol Biomed"},{"issue":"8","key":"5478_CR24","doi-asserted-by":"publisher","first-page":"e2207263120","DOI":"10.1073\/pnas.2207263120","volume":"120","author":"Y Lu","year":"2023","unstructured":"Lu Y, Shimada K, Tang S et al (2023) 1700029I15Rik orchestrates the biosynthesis of acrosomal membrane proteins required for sperm-egg interaction. PNAS 120(8):e2207263120. https:\/\/doi.org\/10.1073\/pnas.2207263120","journal-title":"PNAS"},{"issue":"24","key":"5478_CR25","doi-asserted-by":"publisher","first-page":"18928","DOI":"10.1074\/jbc.M110.107201","volume":"285","author":"A Kraus","year":"2010","unstructured":"Kraus A, Groenendyk J, Bedard K et al (2010) Calnexin deficiency leads to dysmyelination. J Biol Chem 285(24):18928\u201318938. https:\/\/doi.org\/10.1074\/jbc.M110.107201","journal-title":"J Biol Chem"},{"issue":"8","key":"5478_CR26","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1128\/MCB.00038-14","volume":"34","author":"J Schneppenheim","year":"2014","unstructured":"Schneppenheim J, H\u00fcttl S, Mentrup T et al (2014) The intramembrane proteases signal peptide peptidase-like 2a and 2b have distinct functions in vivo. Mol Cell Biol 34(8):1398\u20131411. https:\/\/doi.org\/10.1128\/MCB.00038-14","journal-title":"Mol Cell Biol"},{"key":"5478_CR27","doi-asserted-by":"publisher","unstructured":"Paskevicius T, Farraj RA, Michalak M et al (2023) Calnexin, more Than just a molecular chaperone. Cells 12(3). https:\/\/doi.org\/10.3390\/cells12030403","DOI":"10.3390\/cells12030403"},{"issue":"24","key":"5478_CR28","doi-asserted-by":"publisher","first-page":"e110959","DOI":"10.15252\/embj.2022110959","volume":"41","author":"N Bloemeke","year":"2022","unstructured":"Bloemeke N, Meighen-Berger K, Hitzenberger M et al (2022) Intramembrane client recognition potentiates the chaperone functions of calnexin. EMBO J 41(24):e110959. https:\/\/doi.org\/10.15252\/embj.2022110959","journal-title":"EMBO J"},{"issue":"6633","key":"5478_CR29","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/42484","volume":"387","author":"M Ikawa","year":"1997","unstructured":"Ikawa M, Wada I, Kominami K et al (1997) The putative chaperone calmegin is required for sperm fertility. Nature 387(6633):607\u2013611. https:\/\/doi.org\/10.1038\/42484","journal-title":"Nature"},{"issue":"1","key":"5478_CR30","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1006\/dbio.2001.0462","volume":"240","author":"M Ikawa","year":"2001","unstructured":"Ikawa M, Nakanishi T, Yamada S et al (2001) Calmegin is required for fertilin alpha\/beta heterodimerization and sperm fertility. Dev Biol 240(1):254\u2013261. https:\/\/doi.org\/10.1006\/dbio.2001.0462","journal-title":"Dev Biol"},{"issue":"2","key":"5478_CR31","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1006\/dbio.2002.0803","volume":"250","author":"K Yamagata","year":"2002","unstructured":"Yamagata K, Nakanishi T, Ikawa M et al (2002) Sperm from the calmegin-deficient mouse have normal abilities for binding and fusion to the egg plasma membrane. Dev Biol 250(2):348\u2013357","journal-title":"Dev Biol"},{"key":"5478_CR32","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16968","author":"S H\u00f6ppner","year":"2023","unstructured":"H\u00f6ppner S, Schr\u00f6der B, Fluhrer R (2023) Structure and function of SPP\/SPPL proteases: insights from biochemical evidence and predictive modeling. FEBS J. https:\/\/doi.org\/10.1111\/febs.16968","journal-title":"FEBS J"},{"issue":"10","key":"5478_CR33","doi-asserted-by":"publisher","first-page":"107819","DOI":"10.1016\/j.isci.2023.107819","volume":"26","author":"N Leinung","year":"2023","unstructured":"Leinung N, Mentrup T, Patel M et al (2023) Dynamic association of the intramembrane proteases SPPL2a\/b and their substrates with tetraspanin-enriched microdomains. iScience 26(10):107819. https:\/\/doi.org\/10.1016\/j.isci.2023.107819","journal-title":"iScience"},{"issue":"8","key":"5478_CR34","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1038\/ncb1450","volume":"8","author":"R Fluhrer","year":"2006","unstructured":"Fluhrer R, Grammer G, Israel L et al (2006) A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b. Nat Cell Biol 8(8):894\u2013896. https:\/\/doi.org\/10.1038\/ncb1450","journal-title":"Nat Cell Biol"},{"issue":"11","key":"5478_CR35","doi-asserted-by":"publisher","first-page":"6382","DOI":"10.1073\/pnas.1037392100","volume":"100","author":"WT Kimberly","year":"2003","unstructured":"Kimberly WT, LaVoie MJ, Ostaszewski BL et al (2003) Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci U S A 100(11):6382\u20136387. https:\/\/doi.org\/10.1073\/pnas.1037392100","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"5478_CR36","doi-asserted-by":"publisher","first-page":"6471","DOI":"10.1074\/jbc.M409106200","volume":"280","author":"A Capell","year":"2005","unstructured":"Capell A, Beher D, Prokop S et al (2005) Gamma-secretase complex assembly within the early secretory pathway. J Biol Chem 280(8):6471\u20136478. https:\/\/doi.org\/10.1074\/jbc.M409106200","journal-title":"J Biol Chem"},{"issue":"2","key":"5478_CR37","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1111\/j.1600-0854.2009.01014.x","volume":"11","author":"M Fassler","year":"2010","unstructured":"Fassler M, Zocher M, Klare S et al (2010) Masking of transmembrane-based retention signals controls ER export of gamma-secretase. Traffic 11(2):250\u2013258. https:\/\/doi.org\/10.1111\/j.1600-0854.2009.01014.x","journal-title":"Traffic"},{"issue":"20","key":"5478_CR38","doi-asserted-by":"publisher","first-page":"4322","DOI":"10.1111\/febs.15330","volume":"287","author":"G Kozlov","year":"2020","unstructured":"Kozlov G, Gehring K (2020) Calnexin cycle - structural features of the ER chaperone system. FEBS J 287(20):4322\u20134340. https:\/\/doi.org\/10.1111\/febs.15330","journal-title":"FEBS J"},{"issue":"1","key":"5478_CR39","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/s0092-8674(00)81855-3","volume":"88","author":"A Zapun","year":"1997","unstructured":"Zapun A, Petrescu SM, Rudd PM et al (1997) Conformation-independent binding of monoglucosylated ribonuclease B to calnexin. Cell 88(1):29\u201338. https:\/\/doi.org\/10.1016\/s0092-8674(00)81855-3","journal-title":"Cell"},{"issue":"6440","key":"5478_CR40","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/364771a0","volume":"364","author":"WJ Ou","year":"1993","unstructured":"Ou WJ, Cameron PH, Thomas DY et al (1993) Association of folding intermediates of glycoproteins with calnexin during protein maturation. Nature 364(6440):771\u2013776. https:\/\/doi.org\/10.1038\/364771a0","journal-title":"Nature"},{"issue":"9","key":"5478_CR41","doi-asserted-by":"publisher","first-page":"2904","DOI":"10.1016\/j.bbagen.2014.04.012","volume":"1840","author":"M Sakono","year":"2014","unstructured":"Sakono M, Seko A, Takeda Y et al (2014) Glycan specificity of a testis-specific lectin chaperone calmegin and effects of hydrophobic interactions. Biochim Biophys Acta 1840(9):2904\u20132913. https:\/\/doi.org\/10.1016\/j.bbagen.2014.04.012","journal-title":"Biochim Biophys Acta"},{"issue":"5","key":"5478_CR42","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1095\/biolreprod.106.052977","volume":"75","author":"R Yamaguchi","year":"2006","unstructured":"Yamaguchi R, Yamagata K, Ikawa M et al (2006) Aberrant distribution of ADAM3 in sperm from both angiotensin-converting enzyme (Ace)- and calmegin (Clgn)-deficient mice. Biol Reprod 75(5):760\u2013766. https:\/\/doi.org\/10.1095\/biolreprod.106.052977","journal-title":"Biol Reprod"},{"issue":"15","key":"5478_CR43","doi-asserted-by":"publisher","first-page":"3221","DOI":"10.1242\/dev.094854","volume":"140","author":"N Inoue","year":"2013","unstructured":"Inoue N, Hamada D, Kamikubo H et al (2013) Molecular dissection of IZUMO1, a sperm protein essential for sperm-egg fusion. Development 140(15):3221\u20133229. https:\/\/doi.org\/10.1242\/dev.094854","journal-title":"Development"},{"issue":"1","key":"5478_CR44","doi-asserted-by":"publisher","first-page":"5335","DOI":"10.1038\/s41598-020-62091-y","volume":"10","author":"S Barbaux","year":"2020","unstructured":"Barbaux S, Ialy-Radio C, Chalbi M et al (2020) Sperm SPACA6 protein is required for mammalian sperm-Egg Adhesion\/Fusion. Sci Rep 10(1):5335. https:\/\/doi.org\/10.1038\/s41598-020-62091-y","journal-title":"Sci Rep"},{"issue":"21","key":"5478_CR45","doi-asserted-by":"publisher","first-page":"11493","DOI":"10.1073\/pnas.1922650117","volume":"117","author":"T Noda","year":"2020","unstructured":"Noda T, Lu Y, Fujihara Y et al (2020) Sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm-oocyte fusion in mice. PNAS 117(21):11493\u201311502. https:\/\/doi.org\/10.1073\/pnas.1922650117","journal-title":"PNAS"},{"issue":"7","key":"5478_CR46","doi-asserted-by":"publisher","first-page":"437","DOI":"10.22074\/CELLJ.2023.1983074.1205","volume":"25","author":"M Rahmani","year":"2023","unstructured":"Rahmani M, Tavalaee M, R Drevet J et al (2023) Role of endoplasmic reticulum stress in the male Reproductive System. Cell J 25(7):437\u2013446. https:\/\/doi.org\/10.22074\/CELLJ.2023.1983074.1205","journal-title":"Cell J"},{"issue":"3","key":"5478_CR47","doi-asserted-by":"publisher","first-page":"e14350","DOI":"10.1111\/and.14350","volume":"54","author":"R Yu","year":"2022","unstructured":"Yu R, Chen X, Zhu X et al (2022) ATF6 deficiency damages the development of spermatogenesis in male Atf6 knockout mice. Andrologia 54(3):e14350. https:\/\/doi.org\/10.1111\/and.14350","journal-title":"Andrologia"},{"key":"5478_CR48","doi-asserted-by":"publisher","unstructured":"Inoue N, Hagihara Y, Wada I (2021) Evolutionarily conserved sperm factors, DCST1 and DCST2, are required for gamete fusion. eLife 10. https:\/\/doi.org\/10.7554\/eLife.66313","DOI":"10.7554\/eLife.66313"},{"issue":"D1","key":"5478_CR49","doi-asserted-by":"publisher","first-page":"D442","DOI":"10.1093\/nar\/gky1106","volume":"47","author":"Y Perez-Riverol","year":"2019","unstructured":"Perez-Riverol Y, Csordas A, Bai J et al (2019) The PRIDE database and related tools and resources in 2019: improving support for quantification data. Nucleic Acids Res 47(D1):D442\u2013D450. https:\/\/doi.org\/10.1093\/nar\/gky1106","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"5478_CR50","doi-asserted-by":"publisher","first-page":"D1145","DOI":"10.1093\/nar\/gkz984","volume":"48","author":"EW Deutsch","year":"2020","unstructured":"Deutsch EW, Bandeira N, Sharma V et al (2020) The ProteomeXchange consortium in 2020: enabling \u2018big data\u2019 approaches in proteomics. Nucleic Acids Res 48(D1):D1145\u2013D1152. https:\/\/doi.org\/10.1093\/nar\/gkz984","journal-title":"Nucleic Acids Res"}],"container-title":["Cellular and Molecular Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00018-024-05478-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00018-024-05478-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00018-024-05478-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T17:01:51Z","timestamp":1729962111000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00018-024-05478-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,26]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["5478"],"URL":"https:\/\/doi.org\/10.1007\/s00018-024-05478-8","relation":{},"ISSN":["1420-682X","1420-9071"],"issn-type":[{"value":"1420-682X","type":"print"},{"value":"1420-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,26]]},"assertion":[{"value":"12 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 October 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Breeding of mice has been approved by the Landesdirektion Sachsen (TV A 12\/2018, DD24.1-5131\/450\/12; TV vG 5\/2023, 25-5131\/564\/5). Animal experiments including calnexin-deficient mice were carried out according to the University of Alberta Animal Policy and Welfare Committee and the Canadian Council on Animal Care Guidelines. The approval for use of animals in research was granted by the Animal Care and Use Committee for Health Science, a University of Alberta ethics review committee (AUP297 and 409).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"441"}}