Department of Genetics, Rutgers University, the State University of New Jersey, Piscataway, NJ 08854, USA.
Curr Biol. 2009 Oct 13;19(19):1599-607. doi: 10.1016/j.cub.2009.08.045. Epub 2009 Sep 24.
C. elegans male sexual behaviors include chemotaxis and response to hermaphrodites, backing, turning, vulva location, spicule insertion, and sperm transfer, culminating in cross-fertilization of hermaphrodite oocytes with male sperm. The LOV-1 and PKD-2 transient receptor potential polycystin (TRPP) complex localizes to ciliated endings of C. elegans male-specific sensory neurons and mediates several aspects of male mating behavior. TRPP complex ciliary localization and sensory function are evolutionarily conserved. A genetic screen for C. elegans mutants with PKD-2 ciliary localization (Cil) defects led to the isolation of a mutation in the cil-1 gene.
Here, we report that a phosphoinositide (PI) 5-phosphatase, CIL-1, regulates TRPP complex ciliary receptor localization and sperm activation. cil-1 does not regulate the localization of other ciliary proteins, including intraflagellar transport (IFT) components, sensory receptors, or other TRP channels in different cell types. Rather, cil-1 specifically controls TRPP complex trafficking in male-specific sensory neurons and does so in a cell-autonomous fashion. In these cells, cil-1 is required for normal PI(3)P distribution, indicating that a balance between PI(3,5)P2 and PI(3)P is important for TRPP localization. cil-1 mutants are infertile because of sperm activation and motility defects. In sperm, the CIL-1 5-phosphatase and a wortmannin-sensitive PI 3-kinase act antagonistically to regulate the conversion of sessile spermatids into motile spermatozoa, implicating PI(3,4,5)P3 signaling in nematode sperm activation.
Our studies identify the CIL-1 5-phosphatase as a key regulator of PI metabolism in cell types that are important in several aspects of male reproductive biology.
秀丽隐杆线虫雄性性行为包括化学趋向性和对雌雄同体的反应、倒退、转身、阴道定位、刺突插入和精子转移，最终导致雌雄同体卵子与雄性精子的异配受精。 LOV-1 和 PKD-2 瞬时受体电位多聚体阳离子通道 (TRPP) 复合物定位于秀丽隐杆线虫雄性特异性感觉神经元的纤毛末端，并介导雄性交配行为的几个方面。TRPP 复合物纤毛定位和感觉功能在进化上是保守的。秀丽隐杆线虫 PKD-2 纤毛定位 (Cil) 缺陷突变体的遗传筛选导致 cil-1 基因的突变。
本文报道了一种磷酸肌醇 (PI) 5-磷酸酶 CIL-1，它调节 TRPP 复合物纤毛受体定位和精子激活。 cil-1 不调节其他纤毛蛋白的定位，包括鞭毛内运输 (IFT) 成分、感觉受体或不同细胞类型中的其他 TRP 通道。相反， cil-1 特异性地控制雄性特异性感觉神经元中 TRPP 复合物的运输，并且以细胞自主的方式进行。在这些细胞中， cil-1 是正常 PI(3)P 分布所必需的，这表明 PI(3,5)P2 和 PI(3)P 之间的平衡对于 TRPP 定位很重要。 cil-1 突变体由于精子激活和运动缺陷而不育。在精子中， CIL-1 5-磷酸酶和一种 wortmannin 敏感的 PI 3-激酶相互拮抗，调节固着的精细胞向游动精子的转化，表明 PI(3,4,5)P3 信号在线虫精子激活中起作用。
我们的研究确定了 CIL-1 5-磷酸酶作为细胞类型中 PI 代谢的关键调节剂，这些细胞类型在雄性生殖生物学的几个方面都很重要。
