HIPK4 is essential for murine spermiogenesis

Mammalian spermiogenesis is a remarkable cellular transformation, during which round spermatids elongate into chromatin-condensed spermatozoa. The signaling pathways that coordinate this process are poorly understood, and here we demonstrate that homeodomain-interacting protein kinase 4 (HIPK4) is required for sperm head shaping and male fertility in mice. HIPK4 is expressed in round and early elongating spermatids. Hipk4 knockout males are sterile, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. Mutant sperm have reduced oocyte binding and are incompetent for in vitro fertilization, but can produce viable offspring via intracytoplasmic sperm injection. Ultrastructural analyses of HIPK4-null male germ cells reveal defects in the filamentous actin (F-actin)-scaffolded acroplaxome during spermatid elongation and abnormal head morphologies in mature spermatozoa. We further observe that HIPK4 overexpression induces branched F-actin structures in cultured fibroblasts, sup...

哺乳动物精子形成是一种显著的细胞转化过程，期间圆形精子细胞伸长为染色质浓缩的精子。目前对于协调该过程的信号通路仍知之甚少，本研究证实，同源结构域相互作用蛋白激酶4（homeodomain-interacting protein kinase 4，HIPK4）对小鼠精子头部塑形与雄性生育能力不可或缺。HIPK4在圆形精子细胞及早期伸长型精子细胞中表达。Hipk4基因敲除雄性小鼠不育，其表型与少弱畸精子症（oligoasthenoteratozoospermia）相符。突变精子的卵母细胞结合能力下降，无法完成体外受精，但可通过卵胞浆内单精子注射（intracytoplasmic sperm injection，ICSI）产下可存活后代。对HIPK4敲除雄性生殖细胞的超微结构分析显示，精子细胞伸长过程中，由丝状肌动蛋白（filamentous actin，F-actin）构成支架的顶体小体存在结构缺陷，成熟精子亦出现头部形态异常。我们进一步观察到，在培养的成纤维细胞中过表达HIPK4可诱导分支状F-actin结构，原文此处未完结