Phosphatidylinositol 4-Phosphate 5-Kinase Is Indispensable for Mouse Spermatogenesis
Phosphatidylinositol 4-Phosphate 5-Kinase Is Indispensable for Mouse Spermatogenesis
复制标题
DOI：
10.1095/biolreprod.110.089896
复制
发表时间：
2012-05-01
影响因子：
3.6
通讯作者：
Kanaho, Yasunori
中科院分区：
文献类型：
--
作者：
Hasegawa, Hiroshi;Noguchi, Junko;Kanaho, Yasunori
磷脂酰肌醇-4-磷酸-5-激酶(PIP5K)是一种能产生多种信号的磷脂，即磷脂酰肌醇-4，5-二磷酸。到目前为止，已在哺乳动物中鉴定出三种PIP5K同工酶，即PIP5K1A、PIP5K1B和PIP5K1C。虽然这三种PIP5K同工酶的功能在体外已经得到了广泛的研究，但这些PIP5K同工酶在体内的生理作用仍然很大程度上是未知的。本研究利用PIP5K1a基因敲除小鼠(KO)、PIP5K1b基因敲除小鼠(PIP5K1b-KO)和PIP5K1a/PIP5K1b双(D)-KO小鼠，研究了PIP5K1a和PIP5K1B在精子发生中的作用。PIP5K1A-KO和D-KO分别为次可育和完全不育。D-KO组小鼠生精上皮中的F-肌动蛋白排列紊乱，但顶端外质特化处的F-肌动蛋白束未受影响。D-KO曲细精管中的细长精子细胞数量显著减少。PIP5K1a-KO和D-KO小鼠的精子鞭毛发生了明显的形态变化，而PIP5K1b-KO小鼠的精子形态正常。值得注意的是，D-KO精子的鞭毛形状受损程度比PIP5K1a-KO精子严重。这些结果表明，PIP5K1A和PIP5K1B在精子发生过程中可能协同和/或冗余地维持精子的数量和形态。
The lipid kinase phosphatidylinositol 4-phosphate 5-kinase (PIP5K) produces a versatile signaling phospholipid, phosphatidylinositol 4,5-bisphosphate. Three PIP5K isozymes, PIP5K1A, PIP5K1B, and PIP5K1C, have been identified in mammals so far. Although the functions of these three PIP5K isozymes have been extensively studied in vitro, the in vivo physiological roles of these PIP5K isozymes remain largely unknown. In this study, we examined the functions of PIP5K1A and PIP5K1B in spermatogenesis, using Pip5k1a-knockout (KO), Pip5k1b-KO, and Pip5k1a/Pip5k1b double (D)-KO mice. Pip5k1a-KO and D-KO males were subfertile and completely sterile, respectively. F-actin in the seminiferous epithelium was disorganized in the D-KO mice, although F-actin bundles at the apical ectoplasmic specialization was not affected. D-KO seminiferous tubules contained a greatly decreased number of elongated spermatids. Flagella of sperm from Pip5k1a-KO and D-KO mice remarkably underwent morphological change, whereas Pip5k1b-KO sperm were morphologically normal. Notably, the flagellar shape of D-KO sperm was more severely impaired than that of Pip5k1a-KO sperm. These results suggest that PIP5K1A and PIP5K1B may coordinately and/or redundantly function in the maintenance of sperm number and morphology during spermatogenesis.