The Sept4 septin locus is required for sperm terminal differentiation in mice
The Sept4 septin locus is required for sperm terminal differentiation in mice
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DOI：
10.1016/j.devcel.2005.01.021
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发表时间：
2005-03-01
影响因子：
11.8
通讯作者：
Steller, H
中科院分区：
文献类型：
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作者：
Kissel, H;Georgescu, MM;Steller, H
鼠septin4基因（Sept4）涉及多种细胞功能，包括胞质分裂、细胞凋亡和肿瘤抑制。在这里，我们通过创建Sept4基因组位点的靶向缺失来研究Sept4蛋白在小鼠发育过程中的功能。Sept4突变小鼠是可行的，但雄性不育，由于不动和结构缺陷的精子。在精子发生过程中，Sept4蛋白对于适当的线粒体结构和环（精子尾部区域的环状结构）的建立是必不可少的。此外，Sept4突变精子在精子成熟过程中表现出消除残留细胞质的缺陷，并且对半胱天冬酶抑制剂XIAP的染色增加。这与促凋亡Sept4蛋白ARTS在通过抑制XIAP促进半胱天冬酶介导的细胞质去除中的作用一致。我们的研究结果表明，Sept4蛋白发挥不同的，但在进化上保守的功能，在不同的细胞隔室。
The murine septin4 gene (Sept4) has been implicated in diverse cellular functions, including cytokinesis, apoptosis, and tumor suppression. Here, we investigated the function of Sept4 proteins during mouse development by creating a targeted deletion of the Sept4 genomic locus. Sept4 mutant mice are viable but male sterile due to immotile and structurally defective sperm. During spermatogenesis, Sept4 proteins were essential for proper mitochondrial architecture and establishment of the annulus, a ring-like structure in the tail region of sperm. In addition, Sept4 mutant sperm showed defects in the elimination of residual cytoplasm during sperm maturation and had increased staining for the caspase inhibitor XIAP This is consistent with a role of the proapoptotic Sept4 protein ARTS in promoting caspase-mediated removal of cytoplasm via inhibition of XIAP. Our results indicate that Sept4 proteins play distinct but evolutionarily conserved functions in different cellular compartments.