정진주 (Yale School of Medicine)

한빛사 논문

조회398

Yale School of Medicine

CV File 256 kb

Proc. Natl. Acad. Sci. USA, Sep 26 2023, 120 (39) | https://doi.org/10.1073/pnas.2304409120 A CUG-initiated CATSPERθ functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking.

Xiaofang Huang ¹, Haruhiko Miyata ², Huafeng Wang ¹, Giulia Mori ³, Rie Iida-Norita ², Masahito Ikawa ², Riccardo Percudani ³, Jean-Ju Chung ^{1 4 *}

¹Department of Cellular and Molecular Physiology, Yale School of Medicine, Yale University, New Haven, CT 06510.
²Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
³Department of Chemistry, Life sciences, and Environmental Sustainability, University of Parma, Parma 43124, Italy.
⁴Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, Yale University, New Haven, CT 06510.

^*Corresponding author: correspondence to Jean-Ju Chung

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 (TM) 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 TM subunits results in loss of CATSPERθ protein in the spermatid cells during spermatogenesis. CATSPERθ might act 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.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-09-21)
연구진국외 연구진
분야 생명과학 > 세포생물학

댓글 작성 로그인

CV 열람하기

연락처 보기