8.A.249. Cation Channel Sperm-associated Auxiliary Subunit, TMEM249, (TMEM249) Family
TMEM249 (CATSPERtheta) is an auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation. In the mouse, Slco6c1 is an additional auxiliary subunit of the CatSper complex. It is unclear if the related SLCO6A1 protein performs the same role in non-rodent species. A CUG-initiated CATSPERtheta functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking (Huang et al. 2023). 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. Huang et al. 2023 reported that the Tmem249 -encoded transmembrane domain containing protein, CATSPERtheta, is essential for the CATSPER channel assembly during sperm tail formation. CATSPERtheta facilitates 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 a potential role in CatSper dimer formation. Male mice lacking CATSPERtheta are infertile because 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 CATSPERtheta protein in the spermatid cells during spermatogenesis. CATSPERtheta might acts as a checkpoint for the properly assembled CatSper channel complex to traffic to sperm flagella (Huang et al. 2023). Astrocytes, rather than neurons, diverged in expression of glucose and lactate transmembrane transport, as well as pyruvate processing and oxidative phosphorylation. These findings suggest that astrocytes may have contributed to the evolution of greater brain glucose metabolism in humans. It may explain why the human brain utilizes approximately 20% of all of the body's metabolic resources, while chimpanzee brains use less than 10% (Zintel et al. 2024).
References:
CATSPERtheta (TMEM249) of 235 aas with two TMSs at residues 70 and 100. This subunit seems to be involved in CATSPER assembly (Huang et al. 2023). See family description for details.
CATSPERtheta (TMEM2409 of Homo sapiens
Uncharacterized protein of 233 aas and 2 or 3 TMSs, one (small peak of hydrophobicity) at the N-terminus, and two larger peaks, likely to be TMSs, at residues 70 and 100.
UP of Entophlyctis helioformis
Transmembrane protein 249-like protein of 309 aas and 2 TMSs, TMEM249.
TMEM249 of Folsomia candida
Uncharacterized protein of 180 aas and 2 or 3 TMSs, two at residues 70 and 90, and one at the C-terminus of the protein.
UP of Holothuria leucospilota
Uncharacterized protein of 186 aas and possibly 3 TMSs, at residues 35 and 70 as well as C-terminal.
UP of Dendronephthya gigantea