Fenker Kristin E, Hansen Angela A, Chong Conrad A, Jud Molly C, Duffy Brittany A, Norton J Paul, Hansen Jody M, Stanfield Gillian M
Department of Human Genetics, University of Utah, 15 North 2030 East, Room 6110B, Salt Lake City, UT 84112, USA.
Department of Human Genetics, University of Utah, 15 North 2030 East, Room 6110B, Salt Lake City, UT 84112, USA.
Dev Biol. 2014 Sep 1;393(1):171-82. doi: 10.1016/j.ydbio.2014.06.001. Epub 2014 Jun 12.
Motility of sperm is crucial for their directed migration to the egg. The acquisition and modulation of motility are regulated to ensure that sperm move when and where needed, thereby promoting reproductive success. One specific example of this phenomenon occurs during differentiation of the ameboid sperm of Caenorhabditis elegans as they activate from a round spermatid to a mature, crawling spermatozoon. Sperm activation is regulated by redundant pathways to occur at a specific time and place for each sex. Here, we report the identification of the solute carrier 6 (SLC6) transporter protein SNF-10 as a key regulator of C. elegans sperm activation in response to male protease activation signals. We find that SNF-10 is present in sperm and is required for activation by the male but not by the hermaphrodite. Loss of both snf-10 and a hermaphrodite activation factor render sperm completely insensitive to activation. Using in vitro assays, we find that snf-10 mutant sperm show a specific deficit in response to protease treatment but not to other activators. Prior to activation, SNF-10 is present in the plasma membrane, where it represents a strong candidate to receive signals that lead to subcellular morphogenesis. After activation, it shows polarized localization to the cell body region that is dependent on membrane fusions mediated by the dysferlin FER-1. Our discovery of snf-10 offers insight into the mechanisms differentially employed by the two sexes to accomplish the common goal of producing functional sperm, as well as how the physiology of nematode sperm may be regulated to control motility as it is in mammals.
精子的运动能力对于它们向卵子的定向迁移至关重要。运动能力的获得和调节受到调控,以确保精子在需要的时间和地点移动,从而促进生殖成功。这种现象的一个具体例子发生在秀丽隐杆线虫的阿米巴样精子分化过程中,它们从圆形精子细胞激活成为成熟的、爬行的精子。精子激活由冗余途径调节,在每个性别特定的时间和地点发生。在这里,我们报告溶质载体6(SLC6)转运蛋白SNF-10的鉴定,它是秀丽隐杆线虫精子响应雄性蛋白酶激活信号而激活的关键调节因子。我们发现SNF-10存在于精子中,是雄性而非雌雄同体激活所必需的。snf-10和雌雄同体激活因子的缺失使精子对激活完全不敏感。通过体外试验,我们发现snf-10突变体精子对蛋白酶处理有特定缺陷,但对其他激活剂没有。在激活之前,SNF-10存在于质膜中,在那里它是接收导致亚细胞形态发生信号的有力候选者。激活后,它显示出依赖于dysferlin FER-1介导的膜融合的向细胞体区域的极化定位。我们对snf-10的发现为两性为实现产生功能性精子这一共同目标而采用的不同机制提供了见解,也为线虫精子的生理学如何像在哺乳动物中那样被调节以控制运动能力提供了见解。