Bug22 influences cilium morphology and the post-translational modification of ciliary microtubules.

Bug22 influences cilium morphology and the post-translational modification of ciliary microtubules.
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DOI:
10.1242/bio.20146577
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发表时间:
2014-02-15
期刊:
影响因子:
2.4
通讯作者:
Basto R
Basto R
中科院分区:
生物学4区
文献类型:
--
作者:
Mendes Maia T;Gogendeau D;Pennetier C;Janke C;Basto R

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纤毛和鞭毛是运动和感受环境刺激所必需的细胞器。根据细胞类型,纤毛获得一组定义的功能,并相应地构建有适当的长度和分子组成。几种纤毛蛋白在整个进化过程中表现出高度的保守性,纤毛基因的突变与各种疾病如纤毛病和不育有关。在这里,我们描述的高度保守的纤毛蛋白,Bug22,在果蝇的作用。以前在单细胞生物中的研究表明,Bug22是正常纤毛功能所必需的,但其在纤毛发生中的确切作用尚未研究。EscherichBug22突变果蝇显示纤毛相关表型和神经系统缺陷。此外,由于个体化机制的迁移受损,精子分化在个体化阶段受阻。微管蛋白的翻译后修饰(PTM),如多聚甘氨酰化,多聚谷氨酰化或乙酰化,是微管(MT)的功能和稳定性的中心粒,纤毛和神经元的决定因素。我们发现Bug 22突变体的精子轴丝MT中多糖基化的及时掺入存在缺陷。此外,我们发现,在RPE 1细胞中的人Bug22的耗尽导致更长的纤毛和减少的轴丝多聚谷氨酰胺化的外观。我们的工作确定Bug22作为一种蛋白质,在睫状体轴丝的PTM的调节中起着保守的作用。
Cilia and flagella are organelles essential for motility and sensing of environmental stimuli. Depending on the cell type, cilia acquire a defined set of functions and, accordingly, are built with an appropriate length and molecular composition. Several ciliary proteins display a high degree of conservation throughout evolution and mutations in ciliary genes are associated with various diseases such as ciliopathies and infertility. Here, we describe the role of the highly conserved ciliary protein, Bug22, in Drosophila. Previous studies in unicellular organisms have shown that Bug22 is required for proper cilia function, but its exact role in ciliogenesis has not been investigated yet. Null Bug22 mutant flies display cilia-associated phenotypes and nervous system defects. Furthermore, sperm differentiation is blocked at the individualization stage, due to impaired migration of the individualization machinery. Tubulin post-translational modifications (PTMs) such as polyglycylation, polyglutamylation or acetylation, are determinants of microtubule (MT) functions and stability in centrioles, cilia and neurons. We found defects in the timely incorporation of polyglycylation in sperm axonemal MTs of Bug22 mutants. In addition, we found that depletion of human Bug22 in RPE1 cells resulted in the appearance of longer cilia and reduced axonemal polyglutamylation. Our work identifies Bug22 as a protein that plays a conserved role in the regulation of PTMs of the ciliary axoneme.
果蝇 chibby 是基体形成和纤毛发生所必需的,但不是 Wg 信号传导所必需的。
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影响因子: --
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