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PreprintCited by 21Sperm and Testicular FunctionIon channel regulation and functionIon Channels and Receptors

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

A CUG-initiated CATSPERθ functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking

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Huang, Xiaofang, Miyata, Haruhiko, Wang, Huafeng, Mori, Giulia, Iida-Norita, Rie, Ikawa, Masahito, Percudani, Riccardo, Chung, Jean-Ju·2023·Proceedings of the National Academy of Sciences
DOI 10.1101/2023.03.17.532952PMC PMC10523455

Preprint — published as 10.1073/pnas.2304409120

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Abstract

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 Tmem249 -encoded transmembrane domain containing protein, CATSPERθ, is essential for the CatSper channel assembly during sperm tail formation. CATSPERθ facilitates the channel assembly by serving as a scaffold for a pore forming subunit CATSPER4. CATSPERθ 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 CATSPERθ 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 CATSPERθ protein in the spermatid cells during spermatogenesis. CATSPERθ 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 CATSPERθ in sperm motility and male fertility.

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Metadata

Authors
Huang, X., Miyata, H., Wang, H., Mori, G., Iida-Norita, R., Ikawa, M., Percudani, R., & Chung, J.-J.
Affiliations
  • Yale University (US)
  • Research Institute for Microbial Diseases, The University of Osaka (JP)
  • University of Parma (IT)
Corresponding author
Chung, Jean-Ju
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
openRxiv
Published
2023-03-17
Volume
120
Issue
39
Pages
e2304409120-e2304409120
ISSN
0027-8424 (ISSN-L)
DOI
10.1101/2023.03.17.532952
PMC
PMC10523455
OpenAlex
W4386859251
Cited by
21
References
1
Citations by year
2026: 8 · 2025: 5 · 2024: 4 · 2023: 4
FWCI
5.03
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
  • Yale University
  • Grantham Foundation for the Protection of the Environment
  • Lalor Foundation
  • Ministry of Education, Culture, Sports, Science and Technology (JP19H05750, R01HD088412, and JP21H05033, JP22H03214, JP21H05033)
  • Ministero dell’Istruzione, dell’Università e della Ricerca (2017483NH8)
  • Japan Society for the Promotion of Science (19H05750, 23K24473, JP19H05750, JP22H03214, 21H05033)
  • National Institute of Child Health and Human Development
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD087157, R01HD088412, R01HD096745)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords
CatSper, CatSper channel, sperm flagella, channel assembly, sperm motility, male fertility, calcium signaling, spermatogenesis, hyperactivated motility, CUG codon

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