The Seckel syndrome and centrosomal protein Ninein localizes asymmetrically to stem cell centrosomes but is not required for normal development, behavior, or DNA damage response in Drosophila.
The Seckel syndrome and centrosomal protein Ninein localizes asymmetrically to stem cell centrosomes but is not required for normal development, behavior, or DNA damage response in Drosophila.
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DOI：
10.1091/mbc.e15-09-0655
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发表时间：
2016-06-01
影响因子：
3.3
通讯作者：
Megraw TL
中科院分区：
文献类型：
--
作者：
Zheng Y;Mennella V;Marks S;Wildonger J;Elnagdi E;Agard D;Megraw TL
Ninein与微管调节因子γ-微管蛋白结合，调节微管组装，并定位于果蝇的中心体和非中心体微管组织中心。Ninein定位于干细胞中心体不对称，与女儿中心体的偏见。值得注意的是，Ninein是发育，生育力或生存能力的标志。Ninein（Nin）是一种中心体蛋白，其基因在Seckel综合征（SCKL，MIM 210600）中发生突变，这是一种导致原始侏儒症、认知缺陷和对遗传毒性应激敏感性增加的遗传隐性疾病。Nin调节哺乳动物神经干细胞的自我更新，核迁移和微管组装。Nin在进化上是保守的，但其在细胞分裂和发育中的作用尚未在模式生物中研究。在这里，我们的特点是在果蝇的单一Nin直系同源。果蝇Nin定位于中心体的外围，但不像哺乳动物那样定位于中心粒结构。然而，Nin具有促进微管组装的哺乳动物直向同源物的性质。在神经干细胞和生殖系干细胞中，Nin不对称地定位于年轻（子代）中心体，但它不是干细胞不对称分裂所必需的。在翅上皮和肌肉中，Nin定位于非中心体微管组织中心。令人惊讶的是，nin突变体的nin表达缺失不会显著影响突变果蝇的胚胎和脑发育、生育力或运动性能或它们在暴露于DNA损伤剂时的存活。虽然这不是必需的，我们的数据表明，Nin起着支持作用，在中心体和外中心体微管组织和不对称干细胞分裂。
Ninein associates with the microtubule regulator γ-tubulin, regulates microtubule assembly, and localizes to centrosomes and noncentrosomal microtubule-organizing centers in Drosophila. Ninein localizes to stem cell centrosomes asymmetrically, with a bias for the daughter centrosome. Remarkably, Ninein is dispensable for development, fertility, or viability. Ninein (Nin) is a centrosomal protein whose gene is mutated in Seckel syndrome (SCKL, MIM 210600), an inherited recessive disease that results in primordial dwarfism, cognitive deficiencies, and increased sensitivity to genotoxic stress. Nin regulates neural stem cell self-renewal, interkinetic nuclear migration, and microtubule assembly in mammals. Nin is evolutionarily conserved, yet its role in cell division and development has not been investigated in a model organism. Here we characterize the single Nin orthologue in Drosophila. Drosophila Nin localizes to the periphery of the centrosome but not at centriolar structures as in mammals. However, Nin shares the property of its mammalian orthologue of promoting microtubule assembly. In neural and germline stem cells, Nin localizes asymmetrically to the younger (daughter) centrosome, yet it is not required for the asymmetric division of stem cells. In wing epithelia and muscle, Nin localizes to noncentrosomal microtubule-organizing centers. Surprisingly, loss of nin expression from a nin mutant does not significantly affect embryonic and brain development, fertility, or locomotor performance of mutant flies or their survival upon exposure to DNA-damaging agents. Although it is not essential, our data suggest that Nin plays a supportive role in centrosomal and extracentrosomal microtubule organization and asymmetric stem cell division.