| First Author | Huang X | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 39 | Pages | e2304409120 |
| PubMed ID | 37725640 | Mgi Jnum | J:346400 |
| Mgi Id | MGI:7616204 | Doi | 10.1073/pnas.2304409120 |
| Citation | Huang X, et al. (2023) A CUG-initiated CATSPERtheta functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking. Proc Natl Acad Sci U S A 120(39):e2304409120 |
| abstractText | 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, CATSPERtheta is essential for the CatSper channel assembly during sperm tail formation. CATSPERtheta facilitates the channel assembly by serving as a scaffold for a pore-forming subunit CATSPER4. CATSPERtheta 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 CATSPERtheta 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 CATSPERtheta protein in the spermatid cells during spermatogenesis. CATSPERtheta 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 CATSPERtheta in sperm motility and male fertility. |
