Abstract:
Progesterone (P4) acts as a key conserved signalling molecule in vertebrate reproduction. P4 is especially important for mature sperm physiology and subsequent reproductive success. \"CatSpermasome\", a multi-unit molecular complex, has been suggested to be the main if not the only P4-responsive atypical Ca2+-ion channel present in mature sperm. Altogether, here we analyse the protein sequences of CatSper1-4 from more than 500 vertebrates ranging from early fishes to humans. CatSper1 becomes longer in mammals due to sequence gain mainly at the N-terminus. Overall the conservation of full-length CatSper1-4 as well as the individual TM regions remain low. The lipid-water-interface residues (i.e. a 5 amino acid stretch sequence present on both sides of each TM region) also remain highly diverged. No specific patterns of amino acid distributions were observed. The total frequency of positively charged, negatively charged or their ratios do not follow in any specific pattern. Similarly, the frequency of total hydrophobic, total hydrophilic residues or even their ratios remain random and do not follow any specific pattern. We noted that the CatSper1-4 genes are missing in amphibians and the CatSper1 gene is missing in birds. The high variability of CatSper1-4 and gene-loss in certain clades indicate that the \"CatSpermasome\" is not the only P4-responsive ion channel. Data indicate that the molecular evolution of CatSper is mostly guided by diverse hydrophobic ligands rather than only P4. The comparative data also suggest possibilities of other Ca2+-channel/s in vertebrate sperm that can also respond to P4.
摘要:
孕酮(P4)是脊椎动物繁殖中的关键保守信号分子。P4对于成熟的精子生理学和随后的生殖成功尤其重要。\"CatSpermasome\",多单元分子复合物,已被认为是成熟精子中存在的主要(如果不是唯一的)P4反应性非典型Ca2离子通道。总之,在这里,我们分析了从早期鱼类到人类的500多种脊椎动物的CatSper1-4的蛋白质序列。CatSper1在哺乳动物中由于主要在N末端的序列增益而变得更长。总体上,全长CatSper1-4以及各个TM区域的保守性仍然很低。脂质-水界面残基(即存在于每个TM区两侧的5个氨基酸的序列段)也保持高度分散。没有观察到氨基酸分布的特定模式。带正电荷的总频率,带负电荷或它们的比例不遵循任何特定的模式。同样,总疏水的频率,总的亲水残基或甚至它们的比率保持随机并且不遵循任何特定的模式。我们注意到,两栖动物中的CatSper1-4基因缺失,鸟类中的CatSper1基因缺失。CatSper1-4的高度变异性和某些进化枝的基因丢失表明,“CatSpermasome”不是唯一的P4响应离子通道。数据表明CatSper的分子进化主要由不同的疏水配体而不是仅P4引导。比较数据还表明,脊椎动物精子中其他Ca2通道也可能对P4产生反应。