Essential role of citron kinase in cytokinesis of spermatogenic precursors
Essential role of citron kinase in cytokinesis of spermatogenic precursors
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DOI：
10.1242/jcs.00163
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发表时间：
2002-12-15
影响因子：
4
通讯作者：
Silengo, L
中科院分区：
文献类型：
--
作者：
Di Cunto, F;Imarisio, S;Silengo, L
在精子发生过程中，精原细胞分化的第一个形态学标志是不完全的胞质分裂，然后是稳定的细胞间胞质通讯的组装。这种分化雄性生殖细胞的独特特征在进化过程中高度保守，表明胞质分裂末期的调节是精子发生的一个重要方面。然而，睾丸特异性调控胞质分裂的分子机制仍然是未知的。Citron激酶是一种肌紧张素相关蛋白，在胞质分裂控制中作用于GTPase Rho下游。我们以前报道过，Citron激酶敲除小鼠受到胞质分裂阻滞和特定神经元前体细胞凋亡引起的复杂神经系统综合征的影响。在这份报告中，我们表明，此外，这些小鼠表现出显着的睾丸损伤，胚胎和出生后的未分化的生殖细胞和成熟精母细胞的完全缺乏损失。相比之下，突变雌性的卵巢基本上是正常的。发育分析表明，在突变睾丸中观察到的细胞耗竭是由未分化和分化前体细胞凋亡增加引起的。相同的细胞表现出严重的胞质分裂缺陷，导致多核细胞的产生和凋亡。我们的数据表明，Citron激酶是男性生殖细胞系胞质分裂所必需的。
During spermatogenesis, the first morphological indication of spermatogonia differentiation is incomplete cytokinesis, followed by the assembly of stable intercellular cytoplasmic communications. This distinctive feature of differentiating male germ cells has been highly conserved during evolution, suggesting that regulation of the cytokinesis endgame is a crucial aspect of spermatogenesis. However, the molecular mechanisms underlying testis-specific regulation of cytokinesis are still largely unknown. Citron kinase is a myotonin-related protein acting downstream of the GTPase Rho in cytokinesis control. We previously reported that Citron kinase knockout mice are affected by a complex neurological syndrome caused by cytokinesis block and apoptosis of specific neuronal precursors. In this report we show that, in addition, these mice display a dramatic testicular impairment, with embryonic and postnatal loss of undifferentiated germ cells and complete absence of mature spermatocytes. By contrast, the ovaries of mutant females appear essentially normal. Developmental analysis revealed that the cellular depletion observed in mutant testes is caused by increased apoptosis of undifferentiated and differentiating precursors. The same cells display a severe cytokinesis defect, resulting in the production of multinucleated cells and apoptosis. Our data indicate that Citron kinase is specifically required for cytokinesis of the male germ line.