{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:24:49Z","timestamp":1791599089408,"version":"4.3.4"},"reference-count":55,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"4","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,1,27]]},"abstract":"<jats:p>\n            Spermatozoa need to undergo an exocytotic event called the acrosome reaction before fusing with eggs. Although calcium ion (Ca\n            <jats:sup>2+<\/jats:sup>\n            ) is essential for the acrosome reaction, its molecular mechanism remains unknown. Ferlin is a single transmembrane protein with multiple Ca\n            <jats:sup>2+<\/jats:sup>\n            -binding C2 domains, and there are six ferlins, dysferlin (DYSF), otoferlin (OTOF), myoferlin (MYOF), fer-1\u2013like 4 (FER1L4), FER1L5, and FER1L6, in mammals.\n            <jats:italic>Dysf<\/jats:italic>\n            ,\n            <jats:italic>Otof<\/jats:italic>\n            , and\n            <jats:italic>Myof<\/jats:italic>\n            knockout mice have been generated, and each knockout mouse line exhibited membrane fusion disorders such as muscular dystrophy in\n            <jats:italic>Dysf<\/jats:italic>\n            , deafness in\n            <jats:italic>Otof<\/jats:italic>\n            , and abnormal myogenesis in\n            <jats:italic>Myof<\/jats:italic>\n            . Here, by generating mutant mice of\n            <jats:italic>Fer1l4<\/jats:italic>\n            ,\n            <jats:italic>Fer1l5<\/jats:italic>\n            , and\n            <jats:italic>Fer1l6<\/jats:italic>\n            , we found that only\n            <jats:italic>Fer1l5<\/jats:italic>\n            is required for male fertility.\n            <jats:italic>Fer1l5<\/jats:italic>\n            mutant spermatozoa could migrate in the female reproductive tract and reach eggs, but no acrosome reaction took place. Even a Ca\n            <jats:sup>2+<\/jats:sup>\n            ionophore cannot induce the acrosome reaction in\n            <jats:italic>Fer1l5<\/jats:italic>\n            mutant spermatozoa. These results suggest that FER1L5 is the missing link between Ca\n            <jats:sup>2+<\/jats:sup>\n            and the acrosome reaction.\n          <\/jats:p>","DOI":"10.1126\/sciadv.ade7607","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T18:58:27Z","timestamp":1674673107000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":34,"title":["Testis-enriched ferlin, FER1L5, is required for Ca\n            <sup>2+<\/sup>\n            -activated acrosome reaction and male fertility"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5572-8734","authenticated-orcid":true,"given":"Akane","family":"Morohoshi","sequence":"first","affiliation":[{"name":"Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871 Japan."},{"name":"Graduate School of Medicine, Osaka University, Suita, Osaka 5650871 Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4758-5803","authenticated-orcid":true,"given":"Haruhiko","family":"Miyata","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871 Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1621-5933","authenticated-orcid":true,"given":"Keizo","family":"Tokuhiro","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871 Japan."},{"name":"Institute of Biomedical Science, Kansai Medical University, Hirakata, Osaka 5731191 Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Iida-Norita","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871 Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0260-7861","authenticated-orcid":true,"given":"Taichi","family":"Noda","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871 Japan."},{"name":"Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Kumamoto 8600811 Japan."},{"name":"Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto, Kumamoto 8608555 Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-3507","authenticated-orcid":true,"given":"Yoshitaka","family":"Fujihara","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871 Japan."},{"name":"Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Suita, Osaka 5648565, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9859-6217","authenticated-orcid":true,"given":"Masahito","family":"Ikawa","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871 Japan."},{"name":"Graduate School of Medicine, Osaka University, Suita, Osaka 5650871 Japan."},{"name":"The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 1088639 Japan."},{"name":"Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Osaka 5650871 Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.115.135368"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2016.02.006"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1401910113"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1917595117"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40494"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900889RRR"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204596200"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506825102"},{"key":"e_1_3_3_10_2","first-page":"4985","article-title":"Visualization of the moment of mouse sperm-egg fusion and dynamic localization of IZUMO1","volume":"125","author":"Satouh Y.","year":"2012","unstructured":"Y. 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