{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:21:03Z","timestamp":1791220863558,"version":"4.1.0"},"reference-count":61,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"32","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,8,12]]},"abstract":"<jats:p>Although gamete fusion represents the central event in sexual reproduction, the required protein machinery is poorly defined. In sperm cells, Izumo1 and several Izumo1-associated proteins play an essential role for this process. However, so far, the mechanisms underlying transport and maturation of Izumo1 and its incorporation into high molecular weight complexes are incompletely defined. Here, we provide a detailed characterization of the C11orf94 protein, which we rename Frey, which provides a platform for the assembly of Izumo1 complexes. By retaining Izumo1 in the endoplasmic reticulum, Frey facilitates its incorporation into high molecular weight complexes. To fulfill its function, the unstable Frey protein is stabilized within the catalytic center of an intramembrane protease. Loss of Frey results in reduced assembly of Izumo1 complexes and male infertility due to impaired gamete fusion. Collectively, these findings provide mechanistic insights into the early biogenesis and functional relevance of Izumo1 complexes.<\/jats:p>","DOI":"10.1126\/sciadv.abo6049","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T17:58:21Z","timestamp":1660327101000},"source":"Crossref","is-referenced-by-count":26,"title":["C11orf94\/Frey is a key regulator for male fertility by controlling Izumo1 complex assembly"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5808-0977","authenticated-orcid":true,"given":"Whendy","family":"Contreras","sequence":"first","affiliation":[{"name":"Institute of Physiological Chemistry, Technische Universit\u00e4t Dresden, Dresden, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7174-9954","authenticated-orcid":true,"given":"Caroline","family":"Wieseh\u00f6fer","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University Hospital, University of Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Schreier","sequence":"additional","affiliation":[{"name":"CRISPR-Cas9 Facility, Experimental Center of the Medical Faculty Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Leinung","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry, Technische Universit\u00e4t Dresden, Dresden, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9216-0065","authenticated-orcid":true,"given":"Petra","family":"Peche","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry, Technische Universit\u00e4t Dresden, Dresden, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-2475","authenticated-orcid":true,"given":"Gunther","family":"Wennemuth","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University Hospital, University of Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4482-6010","authenticated-orcid":true,"given":"Marc","family":"Gentzel","sequence":"additional","affiliation":[{"name":"Core Facility Molecular Analysis\u2013Mass Spectrometry, Center for Molecular and Cellular Bioengineering (CMCB), Technische Universit\u00e4t Dresden, Dresden, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0774-6270","authenticated-orcid":true,"given":"Bernd","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry, Technische Universit\u00e4t Dresden, Dresden, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4570-8734","authenticated-orcid":true,"given":"Torben","family":"Mentrup","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry, Technische Universit\u00e4t Dresden, Dresden, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000953"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.176966"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.22634"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03362"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1530\/REP-13-0193"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.111534"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194809"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13203"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey340"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18596"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-120219-021751"},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","unstructured":"N. G. Brukman K. P. Nakajima C. Valansi X. Li T. Higashiyama B. Podbilewicz IZUMO1 is a sperm fusogen. bioRxiv 478669 [ Preprint ]. 2022; https:\/\/doi.org\/10.1101\/2022.02.01.478669.","DOI":"10.1101\/2022.02.01.478669"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922650117"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.21092"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9858"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-019-0701-1"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-62091-y"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.66313"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.53913"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201846449"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2021.119163"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1406"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2020.05.019"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201948133"},{"key":"e_1_3_3_26_2","first-page":"e61800","article-title":"Transillumination-assisted dissection of specific stages of the mouse seminiferous epithelial cycle for downstream immunostaining analyses","volume":"164","author":"M\u00e4kel\u00e4 J.-A.","year":"2020","unstructured":"J.-A. M\u00e4kel\u00e4, S. Cisneros-Montalvo, T. Lehtiniemi, O. Olotu, H. M. La, J. Toppari, R. M. Hobbs, M. Parvinen, N. Kotaja, Transillumination-assisted dissection of specific stages of the mouse seminiferous epithelial cycle for downstream immunostaining analyses. J. Vis. Exp. 164, e61800 (2020).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.29461"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1917060117"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010301"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2018.1489181"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04163-y"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01124-14"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150940"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1586245"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/27208"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.059"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.190003"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.09.074"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1505649112"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214400"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74275"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2681-2"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09325"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.07.028"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.12.1.27"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7401027"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2009.01014.x"},{"key":"e_1_3_3_48_2","doi-asserted-by":"crossref","unstructured":"Y. Lu K. Shimada J. Zhang Y. Ogawa S. Tang T. Noda H. Shibuya M. Ikawa 1700029I15Rik orchestrates the biosynthesis of acrosomal membrane proteins required for sperm\u2013egg fusion. bioRxiv 488448 [ Preprint ]. 2022; https:\/\/doi.org\/10.1101\/2022.04.15.488448.","DOI":"10.1101\/2022.04.15.488448"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960329)62:3<319::AID-AJMG22>3.0.CO;2-M"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.05.005"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980217)75:5<538::AID-AJMG17>3.0.CO;2-L"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00353"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-010-0412-9"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-010-0378-7"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171438"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1515\/bc.2010.062"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2012.01372.x"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12287"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1106"},{"key":"e_1_3_3_60_2","first-page":"D1145","article-title":"The ProteomeXchange Consortium in 2020: Enabling \u201cbig data\u201d approaches in proteomics","volume":"48","author":"Deutsch E. W.","year":"2020","unstructured":"E. W. Deutsch, N. Bandeira, V. Sharma, Y. Perez-Riverol, J. J. Carver, D. J. Kundu, D. Garc\u00eda-Seisdedos, A. F. Jarnuczak, S. Hewapathirana, B. S. Pullman, J. Wertz, Z. Sun, S. Kawano, S. Okuda, Y. Watanabe, H. Hermjakob, B. Maclean, M. J. MacCoss, Y. Zhu, Y. Ishihama, J. A. Vizca\u00edno, The ProteomeXchange Consortium in 2020: Enabling \u201cbig data\u201d approaches in proteomics. Nucleic Acids Res. 48, D1145\u2013D1152 (2020).","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/jms.465"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.abo6049","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:18:10Z","timestamp":1704835090000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.abo6049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,12]]},"references-count":61,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2022,8,12]]}},"alternative-id":["10.1126\/sciadv.abo6049"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.abo6049","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,12]]},"article-number":"eabo6049"}}