An essential quality control mechanism at the eukaryotic basal body prior to intraflagellar transport
An essential quality control mechanism at the eukaryotic basal body prior to intraflagellar transport
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DOI：
10.1111/j.1600-0854.2007.00611.x
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发表时间：
2007-10-01
期刊：
影响因子：
4.5
通讯作者：
McKean, Paul G.
中科院分区：
文献类型：
--
作者：
Stephan, Angela;Vaughan, Sue;McKean, Paul G.
构建真核纤毛/鞭毛是一项艰巨的任务，需要将蛋白质从其细胞质合成位点转运到空间和环境不同的细胞区室中。明确的潜在危险是，异常蛋白质的输入可能会严重破坏纤毛/鞭毛组装或周转过程。在这里，我们揭示了微管蛋白的目的是纳入轴丝微管相互作用的微管蛋白辅因子C（TBCC）结构域的蛋白质，是专门位于成熟的基体过渡纤维。RNA干扰介导的这种蛋白质的消融导致轴丝微管缺陷，但对细胞内的其他微管群体没有影响。生物信息学分析表明，这种蛋白质属于鞭毛特异性TBCC样蛋白质的一个分支，其中包括人类蛋白质XRP 2，突变导致某些形式的遗传性眼病视网膜色素变性。采取与其他观察过渡纤维在纤毛/鞭毛大会的作用，我们认为，一个本地化的蛋白质加工能力嵌入在过渡纤维，确保“质量”的微管蛋白进口到纤毛/鞭毛，并进一步，纤毛/鞭毛质量控制能力的损失可能会支持一些人类遗传疾病。
Constructing a eukaryotic cilium/flagellum is a demanding task requiring the transport of proteins from their cytoplasmic synthesis site into a spatially and environmentally distinct cellular compartment. The clear potential hazard is that import of aberrant proteins could seriously disable cilia/flagella assembly or turnover processes. Here, we reveal that tubulin protein destined for incorporation into axonemal microtubules interacts with a tubulin cofactor C (TBCC) domain-containing protein that is specifically located at the mature basal body transitional fibres. RNA interference-mediated ablation of this protein results in axonemal microtubule defects but no effect on other microtubule populations within the cell. Bioinformatics analysis indicates that this protein belongs to a clade of flagellum-specific TBCC-like proteins that includes the human protein, XRP2, mutations which lead to certain forms of the hereditary eye disease retinitis pigmentosa. Taken with other observations regarding the role of transitional fibres in cilium/flagellum assembly, we suggest that a localized protein processing capacity embedded at transitional fibres ensures the 'quality' of tubulin imported into the cilium/flagellum, and further, that loss of a ciliary/flagellar quality control capability may underpin a number of human genetic disorders.