Targeted disruption of the Akap4 gene causes defects in sperm flagellum and motility
Targeted disruption of the Akap4 gene causes defects in sperm flagellum and motility
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DOI：
10.1006/dbio.2002.0728
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发表时间：
2002-08-15
影响因子：
2.7
通讯作者：
Eddy, EM
中科院分区：
文献类型：
--
作者：
Miki, K;Willis, WD;Eddy, EM
A激酶锚定蛋白（AKAP）系住环AMP依赖性蛋白激酶，从而定位靶蛋白的磷酸化并启动由环AMP触发的信号转导过程。AKAP也可以是激酶和磷酸酶的支架，并与参与信号转导的其他蛋白质形成大分子复合物。Akap4仅在精子发生的减数分裂后阶段转录，并编码纤维鞘中最丰富的蛋白质，纤维鞘是精子鞭毛主要部分中存在的一种新型细胞骨架结构。以前的研究表明，环AMP依赖的信号传导过程是重要的调节精子活力，基因靶向在这里被用来测试的假设，AKAP 4是一个支架蛋白复合物参与调节鞭毛功能。在缺乏AKAP 4的雄性小鼠中，精子数量没有减少，但精子未能显示出前向运动能力，雄性小鼠不育。纤维鞘原基形成，但最终的纤维鞘没有发展，鞭毛缩短，通常与纤维鞘相关的蛋白质不存在或大量减少。然而，鞭毛的其他细胞骨架成分是存在的，并出现充分发展。我们的结论是AKAP 4是一个支架蛋白所需的组织和完整性的纤维鞘和有效的精子活力在AKAP 4的情况下丢失，因为信号转导和糖酵解酶未能成为相关的纤维鞘。(C)2002 Elsevier Science（美国）。
A-kinase anchoring proteins (AKAPs) tether cyclic AMP-dependent protein kinases and thereby localize phosphorylation of target proteins and initiation of signal-transduction processes triggered by cyclic AMP. AKAPs can also be scaffolds for kinases and phosphatases and form macromolecular complexes with other proteins involved in signal transduction. Akap4 is transcribed only in the postmeiotic phase of spermatogenesis and encodes the most abundant protein in the fibrous sheath, a novel cytoskeletal structure present in the principal piece of the sperm flagellum. Previous studies indicated that cyclic AMP-dependent signaling processes are important in the regulation of sperm motility, and gene targeting was used here to test the hypothesis that AKAP4 is a scaffold for protein complexes involved in regulating flagellar function. Sperm numbers were not reduced in male mice lacking AKAP4, but sperm failed to show progressive motility and male mice were infertile. The fibrous sheath anlagen formed, but the definitive fibrous sheath did not develop, the flagellum was shortened, and proteins usually associated with the fibrous sheath were absent or substantially reduced in amount. However, the other cytoskeletal components of the flagellum were present and appeared fully developed. We conclude that AKAP4 is a scaffold protein required for the organization and integrity of the fibrous sheath and that effective sperm motility is lost in the absence of AKAP4 because signal transduction and glycolytic enzymes fail to become associated with the fibrous sheath. (C) 2002 Elsevier Science (USA).