A novel function for the presenilin family member spe-4: inhibition of spermatid activation in Caenorhabditis elegans.
A novel function for the presenilin family member spe-4: inhibition of spermatid activation in Caenorhabditis elegans.
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DOI：
10.1186/1471-213x-8-44
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发表时间：
2008-04-22
影响因子：
--
通讯作者：
Lamunyon CW
中科院分区：
文献类型：
--
作者：
Gosney R;Liau WS;Lamunyon CW
精子细胞必须调节激活的时间和位置，以最大限度地提高受精的可能性。大多数物种的精子，包括秀丽隐杆线虫，在遇到外部信号时会激活。激活C.秀丽线虫精子发生在精子细胞经历精子发生的过程中，精子发生是一种深刻的细胞重组，产生伪足。精子发生是由一系列基因产物转导的激活信号启动的。现在很清楚，抑制途径也在精子细胞中起作用，防止它们过早地发展为精子，并导致对激活时间的精细控制。在这里，我们描述了一个新分配的成员的抑制途径：SPE-4，人类早老素基因PS1的同源物的参与。spe-4（hc 196）等位基因被分离出来作为精子发生信号转导基因spe-27突变的不育抑制基因。通过作图、互补试验、DNA测序和转化拯救，我们确定等位基因hc 196是spe-4基因中的突变。我们的数据表明spe-4（hc 196）是一个旁路抑制因子，它消除了精子发生信号转导的需要。spe-4（hc 196）本身具有隐性的、温度敏感的精子发生缺陷表型，突变体表现出（i）有缺陷的精母细胞，（ii）有缺陷的精子细胞，（iii）过早的精子细胞激活，和（iv）受精缺陷的精子，此外还有少量显微镜下正常的功能精子。spe-4（hc 196）突变体雄性的精子中有一部分不需要激活信号就能直接发育成有功能的精子，这表明spe-4在阻止精子细胞激活中起作用。spe-4（hc 196）突变体的另一部分精子受精缺陷。因此，过早激活的精子可能有几个缺陷：我们表明，他们可能是有缺陷的受精，早期的工作表明，他们阻碍精子从男性在交配。HC 196是SPE-4的亚型等位基因，其新发现的抑制精子生成的作用可能涉及早老素功能的已知蛋白水解和/或钙调节方面，或者其可能涉及尚未发现的功能。
Sperm cells must regulate the timing and location of activation to maximize the likelihood of fertilization. Sperm from most species, including the nematode Caenorhabditis elegans, activate upon encountering an external signal. Activation for C. elegans sperm occurs as spermatids undergo spermiogenesis, a profound cellular reorganization that produces a pseudopod. Spermiogenesis is initiated by an activation signal that is transduced through a series of gene products. It is now clear that an inhibitory pathway also operates in spermatids, preventing their premature progression to spermatozoa and resulting in fine-scale control over the timing of activation. Here, we describe the involvement of a newly assigned member of the inhibitory pathway: spe-4, a homolog of the human presenilin gene PS1. The spe-4(hc196) allele investigated here was isolated as a suppressor of sterility of mutations in the spermiogenesis signal transduction gene spe-27. Through mapping, complementation tests, DNA sequencing, and transformation rescue, we determined that allele hc196 is a mutation in the spe-4 gene. Our data show that spe-4(hc196) is a bypass suppressor that eliminates the need for the spermiogenesis signal transduction. On its own, spe-4(hc196) has a recessive, temperature sensitive spermatogenesis-defective phenotype, with mutants exhibiting (i) defective spermatocytes, (ii) defective spermatids, (iii) premature spermatid activation, and (iv) spermatozoa defective in fertilization, in addition to a small number of functional sperm which appear normal microscopically. A fraction of the sperm from spe-4(hc196) mutant males progress directly to functional spermatozoa without the need for an activation signal, suggesting that spe-4 plays a role in preventing spermatid activation. Another fraction of spermatozoa from spe-4(hc196) mutants are defective in fertilization. Therefore, prematurely activated spermatozoa may have several defects: we show that they may be defective in fertilization, and earlier work showed that they obstruct sperm transfer from males at mating. hc196 is a hypomorphic allele of spe-4, and its newly-discovered role inhibiting spermiogenesis may involve known proteolytic and/or calcium regulatory aspects of presenilin function, or it may involve yet-to-be discovered functions.