Nuclear mislocalization of enzymatically active RanGAP causes segregation distortion in Drosophila
Nuclear mislocalization of enzymatically active RanGAP causes segregation distortion in Drosophila
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DOI：
10.1016/s1534-5807(01)00042-9
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发表时间：
2001-09-01
影响因子：
11.8
通讯作者：
Ganetzky, B
中科院分区：
文献类型：
--
作者：
Kusano, A;Staber, C;Ganetzky, B
分离扭曲（S，D）是果蝇减数分裂驱动系统，由于SD+精子细胞功能障碍，导致SD/SD+雄性的SO染色体优先传递。Sd基因座，这是必不可少的失真，编码一个截短的RanGAP（Ran GTP酶激活蛋白），一个关键的核转运因子。在这里，我们表明，Sd-RanGAP保留正常的酶活性，但被错误定位到细胞核。当Sd-RanGAP的酶活性或核定位受到干扰时，扭曲被废除。Ran或RanGEF（Ran GT3交换因子）在雄性生殖系中的过表达完全抑制畸变。我们的结论是，Sd-RanGAP的错误定位通过减少核RanGTP导致失真，从而破坏Ran信号通路。唾液腺中GFP报告基因的核转运受到SO的损害，这表明核转运的缺陷可能是精子功能障碍的基础。
Segregation Distorter (S,D) is a meiotic drive system in Drosophila that causes preferential transmission of the SO chromosome from SD/SD+ males owing to dysfunction of SD+ spermatids. The Sd locus, which is essential for distortion, encodes a truncated RanGAP (Ran GTPase activating protein), a key nuclear transport factor. Here, we show that Sd-RanGAP retains normal enzyme activity but is mislocalized to nuclei. Distortion is abolished when enzymatic activity or nuclear localization of Sd-RanGAP is perturbed. Overexpression of Ran or RanGEF (Ran GTPase exchange factor) in the male germline fully suppresses distortion. We conclude that mislocalization of Sd-RanGAP causes distortion by reducing nuclear RanGTP, thereby disrupting the Ran signaling pathway. Nuclear transport of a GFP reporter in salivary glands is impaired by SO, suggesting that a defect in nuclear transport may underlie sperm dysfunction.