{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:37:02Z","timestamp":1768505822829,"version":"3.49.0"},"posted":{"date-parts":[[2023,3,17]]},"group-title":"Cell Biology","reference-count":48,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Calcium signaling is critical for successful fertilization. In spermatozoa, calcium influx into the sperm flagella mediated by the sperm specific CatSper calcium channel is necessary for hyperactivated motility and male fertility. CatSper is a macromolecular complex and is repeatedly arranged in zigzag rows within four linear nanodomains along the sperm flagella. Here, we report that the\n                  <jats:italic>Tmem249<\/jats:italic>\n                  -encoded transmembrane domain containing protein, CATSPER\u03b8, is essential for the CatSper channel assembly during sperm tail formation. CATSPER\u03b8 facilitates the channel assembly by serving as a scaffold for a pore forming subunit CATSPER4. CATSPER\u03b8 is specifically localized at the interface of a CatSper dimer and can self-interact, suggesting its potential role in CatSper dimer formation. Male mice lacking CATSPER\u03b8 are infertile because the sperm lack the entire CatSper channel from sperm flagella, rendering sperm unable to hyperactivate, regardless of their normal expression in the testis. In contrast, genetic abrogation of any of the other CatSper transmembrane subunits results in loss of CATSPER\u03b8 protein in the spermatid cells during spermatogenesis. CATSPER\u03b8 might acts as a checkpoint for the properly assembled CatSper channel complex to traffic to sperm flagella. This study provides insights into the CatSper channel assembly and elucidates the physiological role of CATSPER\u03b8 in sperm motility and male fertility.\n                <\/jats:p>","DOI":"10.1101\/2023.03.17.532952","type":"posted-content","created":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T03:50:01Z","timestamp":1679197801000},"source":"Crossref","is-referenced-by-count":3,"title":["A CUG-initiated CATSPER\u03b8 functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking"],"prefix":"10.64898","author":[{"given":"Xiaofang","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4758-5803","authenticated-orcid":false,"given":"Haruhiko","family":"Miyata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huafeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rie","family":"Iida-Norita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9859-6217","authenticated-orcid":false,"given":"Masahito","family":"Ikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Percudani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8018-1355","authenticated-orcid":false,"given":"Jean-Ju","family":"Chung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023032103501154000_2023.03.17.532952v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1938"},{"key":"2023032103501154000_2023.03.17.532952v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199304293281707"},{"key":"2023032103501154000_2023.03.17.532952v1.3","doi-asserted-by":"crossref","first-page":"999369","DOI":"10.3389\/fphys.2022.999369","article-title":"Ion channel molecular complexes in vascular smooth muscle","volume":"13","year":"2022","journal-title":"Front Physiol"},{"key":"2023032103501154000_2023.03.17.532952v1.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4512-03.2004"},{"key":"2023032103501154000_2023.03.17.532952v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/328313a0"},{"key":"2023032103501154000_2023.03.17.532952v1.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.15.5478"},{"key":"2023032103501154000_2023.03.17.532952v1.7","first-page":"0","article-title":"Kv Channel Ancillary Subunits: Where Do We Go from Here?","volume":"37","year":"2022","journal-title":"Physiology (Bethesda)"},{"key":"2023032103501154000_2023.03.17.532952v1.8","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/s41586-021-03935-z","article-title":"Structural basis of gating modulation of Kv4 channel complexes","volume":"599","year":"2021","journal-title":"Nature"},{"key":"2023032103501154000_2023.03.17.532952v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.10.027"},{"key":"2023032103501154000_2023.03.17.532952v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.09.011"},{"key":"2023032103501154000_2023.03.17.532952v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.12.043"},{"key":"2023032103501154000_2023.03.17.532952v1.12","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.570200"},{"key":"2023032103501154000_2023.03.17.532952v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6535"},{"key":"2023032103501154000_2023.03.17.532952v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2011.10.003"},{"key":"2023032103501154000_2023.03.17.532952v1.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.10.4660"},{"key":"2023032103501154000_2023.03.17.532952v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/35098027"},{"key":"2023032103501154000_2023.03.17.532952v1.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610286104"},{"key":"2023032103501154000_2023.03.17.532952v1.18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.221454998"},{"key":"2023032103501154000_2023.03.17.532952v1.19","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/s41586-021-03742-6","article-title":"Structure of a mammalian sperm cation channel complex","volume":"595","year":"2021","journal-title":"Nature"},{"key":"2023032103501154000_2023.03.17.532952v1.20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701083200"},{"key":"2023032103501154000_2023.03.17.532952v1.21","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.109.077107"},{"key":"2023032103501154000_2023.03.17.532952v1.22","doi-asserted-by":"crossref","unstructured":"J. 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