Mammalian Fused is essential for sperm head shaping and periaxonemal structure formation during spermatogenesis.
Mammalian Fused is essential for sperm head shaping and periaxonemal structure formation during spermatogenesis.
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DOI：
10.1016/j.ydbio.2014.02.002
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发表时间：
2014-04-15
影响因子：
2.7
通讯作者：
Chuang, Pao-Tien
中科院分区：
文献类型：
--
作者：
Nozawa, Yoko Ines;Yao, Erica;Gacayan, Rhodora;Xu, Shan-Mei;Chuang, Pao-Tien
在哺乳动物精子发生过程中，二倍体精原细胞通过高度受控的有丝分裂、减数分裂和减数分裂后形态重塑(精子发生)成熟为单倍体精子。尽管在这一领域取得了重要进展，但支持这种转化的分子机制却知之甚少。我们对可能的丝氨酸-苏氨酸激酶融合(FU)的表达和功能的分析为理解精子发生的关键步骤提供了关键的洞察力。在这份报告中，我们证明了男性生殖细胞中FU的条件灭活会导致精子数量减少、头部形状异常、精子断头和精子运动障碍而导致不育。有趣的是，突变的鞭毛轴丝是完整的，但表现出改变的轴丝周围结构，影响运动性。这些数据表明，FU在精子头的形成和鞭毛中轴突周围结构的组织控制中起着核心作用。我们发现FU定位于多种微管蛋白或微管组织结构，包括与精子细胞头部形成有关的套架和顶体-顶体复合体。此外，FU还与外部致密纤维蛋白Odf1和Kif27相互作用，Odf1是精子鞭毛轴周结构的主要成分，Kif27在套筒中检测到。我们认为，这些结构中的FU功能障碍是FU缺陷精子头部和鞭毛缺陷的基础。由于大多数人类男性不育综合征源于精子活力降低和结构缺陷，揭示FU在精子发生中的作用为理解不育的原因和生殖生物学提供了新的视角。
During mammalian spermatogenesis, the diploid spermatogonia mature into haploid spermatozoa through a highly controlled process of mitosis, meiosis and post-meiotic morphological remodeling (spermiogenesis). Despite important progress made in this area, the molecular mechanisms underpinning this transformation are poorly understood. Our analysis of the expression and function of the putative serine-threonine kinase Fused (Fu) provides critical insight into key steps in spermatogenesis. In this report, we demonstrate that conditional inactivation of Fu in male germ cells results in infertility due to diminished sperm count, abnormal head shaping, decapitation and motility defects of the sperm. Interestingly, mutant flagellar axonemes are intact but exhibit altered periaxonemal structures that affect motility. These data suggest that Fu plays a central role in shaping the sperm head and controlling the organization of the periaxonemal structures in the flagellum. We show that Fu localizes to multiple tubulin-containing or microtubule-organizing structures, including the manchette and the acrosome-acroplaxome complex that are involved in spermatid head shaping. In addition, Fu interacts with the outer dense fiber protein Odf1, a major component of the periaxonemal structures in the sperm flagellum, and Kif27, which is detected in the manchette. We propose that disrupted Fu function in these structures underlies the head and flagellar defects in Fu-deficient sperm. Since a majority of human male infertility syndromes stem from reduced sperm motility and structural defects, uncovering Fu’s role in spermiogenesis provides new insight into the causes of sterility and the biology of reproduction.
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影响因子：
2.5
作者：
Kierszenbaum, Abraham L.;Rivkin, Eugene;Tres, Laura L.;Yoder, Bradley K.;Haycraft, Courtney J.;Bornens, Michel;Rios, Rosa M.
通讯作者：
Rios, Rosa M.
影响因子：
2.5
作者：
Kierszenbaum, AL
通讯作者：
Kierszenbaum, AL
影响因子：
1.5
作者：
Gallardo, Teresa;Shirley, Lane;Castrillon, Diego H.
通讯作者：
Castrillon, Diego H.
影响因子：
2.7
作者：
Moreno, RD;Palomino, J;Schatten, G
通讯作者：
Schatten, G
影响因子：
7.2
作者：
Greenbaum, Michael P.;Iwamori, Tokuko;Matzuk, Martin M.
通讯作者：
Matzuk, Martin M.