Ren D, Navarro B, Perez G, Jackson A C, Hsu S, Shi Q, Tilly J L, Clapham D E
Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nature. 2001 Oct 11;413(6856):603-9. doi: 10.1038/35098027.
Calcium and cyclic nucleotides have crucial roles in mammalian fertilization, but the molecules comprising the Ca2+-permeation pathway in sperm motility are poorly understood. Here we describe a putative sperm cation channel, CatSper, whose amino-acid sequence most closely resembles a single, six-transmembrane-spanning repeat of the voltage-dependent Ca2+-channel four-repeat structure. CatSper is located specifically in the principal piece of the sperm tail. Targeted disruption of the gene results in male sterility in otherwise normal mice. Sperm motility is decreased markedly in CatSper-/- mice, and CatSper-/- sperm are unable to fertilize intact eggs. In addition, the cyclic-AMP-induced Ca2+ influx is abolished in the sperm of mutant mice. CatSper is thus vital to cAMP-mediated Ca2+ influx in sperm, sperm motility and fertilization. CatSper represents an excellent target for non-hormonal contraceptives for both men and women.
钙和环核苷酸在哺乳动物受精过程中起着至关重要的作用,但对于精子运动中构成钙离子渗透途径的分子,我们却知之甚少。在此,我们描述了一种推测的精子阳离子通道CatSper,其氨基酸序列与电压依赖性钙通道四重复结构的单个六跨膜重复结构最为相似。CatSper特异性地位于精子尾部的主段。对该基因进行靶向破坏会导致原本正常的小鼠出现雄性不育。在CatSper基因敲除小鼠中,精子活力显著下降,且CatSper基因敲除小鼠的精子无法使完整的卵子受精。此外,突变小鼠精子中环磷酸腺苷诱导的钙离子内流被消除。因此,CatSper对于精子中由环磷酸腺苷介导的钙离子内流、精子活力和受精过程至关重要。CatSper是男女非激素避孕药物的一个绝佳靶点。