Romero Francisco, Nishigaki Takuya
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología. Universidad Nacional Autónoma de México (IBT-UNAM). Av. Universidad 2001, Col. Chamilpa, 62210 Cuernavaca, Morelos Mexico.
Zoological Lett. 2019 Jul 26;5:25. doi: 10.1186/s40851-019-0141-3. eCollection 2019.
CatSper is a sperm-specific calcium ion (Ca) channel, which regulates sperm flagellar beating by tuning cytoplasmic Ca concentrations. Although this Ca channel is essential for mammalian fertilization, recent bioinformatics analyses have revealed that genes encoding CatSper are heterogeneously distributed throughout the eukaryotes, including vertebrates. As this channel is activated by cytoplasmic alkalization in mammals and sea urchins, it has been proposed that the sperm-specific Na/H exchanger (sNHE, a product of the gene family) positively regulates its activity. In mouse, sNHE is functionally coupled to soluble adenylyl cyclase (sAC). CatSper, sNHE, and sAC have thus been considered functionally interconnected in the control of sperm motility, at least in mouse and sea urchin.
We carried out a comparative genomic analysis to explore phylogenetic relationships among CatSper, sNHE and sAC in eukaryotes. We found that sNHE occurs only in Metazoa, although sAC occurs widely across eukaryotes. In animals, we found correlated and restricted distribution patterns of the three proteins, suggesting coevolution among them in the Metazoa. Namely, nearly all species in which CatSper is conserved also preserve sNHE and sAC. In contrast, in species without sAC, neither CatSper nor sNHE is conserved. On the other hand, the distribution of another testis-specific NHE (NHA, a product of the gene family) does not show any apparent association with that of CatSper.
Our results suggest that CatSper, sNHE and sAC form prototypical machinery that functions in regulating sperm flagellar beating in Metazoa. In non-metazoan species, CatSper may be regulated by other H transporters, or its activity might be independent of cytoplasmic pH.
精子阳离子通道（CatSper）是一种精子特异性钙离子（Ca）通道，通过调节细胞质钙离子浓度来调控精子鞭毛摆动。尽管这种钙离子通道对哺乳动物受精至关重要，但最近的生物信息学分析表明，编码CatSper的基因在包括脊椎动物在内的整个真核生物中分布不均。由于该通道在哺乳动物和海胆中可被细胞质碱化激活，因此有人提出精子特异性钠/氢交换体（sNHE，基因家族的产物）可正向调节其活性。在小鼠中，sNHE在功能上与可溶性腺苷酸环化酶（sAC）偶联。因此，至少在小鼠和海胆中，CatSper、sNHE和sAC被认为在精子运动控制方面存在功能上的相互联系。
我们进行了比较基因组分析，以探索真核生物中CatSper、sNHE和sAC之间的系统发育关系。我们发现sNHE仅出现在后生动物中，而sAC广泛存在于整个真核生物中。在动物中，我们发现这三种蛋白质存在相关且受限的分布模式，表明它们在后生动物中共同进化。也就是说，几乎所有保留CatSper的物种也保留了sNHE和sAC。相反，在没有sAC的物种中，CatSper和sNHE都不保守。另一方面，另一种睾丸特异性NHE（NHA，基因家族的产物）的分布与CatSper的分布没有明显关联。
我们的结果表明，CatSper、sNHE和sAC形成了后生动物中调节精子鞭毛摆动的原型机制。在非后生动物物种中，CatSper可能受其他氢转运体调节，或者其活性可能与细胞质pH无关。
