Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging.
Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging.
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DOI：
10.1371/journal.pgen.1006325
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发表时间：
2016-12
期刊：
影响因子：
4.5
通讯作者：
Sengupta P
中科院分区：
文献类型：
--
作者：
Cornils A;Maurya AK;Tereshko L;Kennedy J;Brear AG;Prahlad V;Blacque OE;Sengupta P
大多数纤毛是通过鞭毛内运输（IFT）的高度保守过程形成和维持的。IFT基因突变导致纤毛结构缺陷和称为纤毛病的系统性疾病。在这里，我们表明，严重截断的感觉纤毛的亚形IFT突变体在C。秀丽线虫在成年衰老的不连续时期短暂伸长，导致明显改善的感觉行为。纤毛形态学的依赖性恢复发生在结构多样的纤毛类型中，并且需要IFT。我们证明，虽然ESTA-16/FOXO是ESTA，年龄依赖性抑制的纤毛表型IFT突变体需要细胞自主功能的HSF 1热休克因子和Hsp 90伴侣。我们的研究结果描述了一个意想不到的作用，早期老化和蛋白质质量控制机制，在抑制纤毛表型IFT突变体，并建议可能的策略，针对亚组的纤毛病变。纤毛是“触角样”结构，存在于动物的几乎所有细胞类型上。这些结构对于感知和向细胞发出外部信号非常重要。大多数纤毛是由蛋白质运输过程形成的，称为“鞭毛内运输”或IFT。IFT基因的突变导致严重的纤毛缺陷，并且是大量不同的人类疾病（称为纤毛病）的原因。由于纤毛形成的基因和过程在物种间是相似的，因此在实验模型中的研究，如线虫C。elegans可以极大地告知我们纤毛的形成和功能的整体理解。在这里，我们报告了令人惊讶的观察结果，严重缺陷的纤毛的结构和功能的线虫与破坏IFT基因显着改善老化。我们发现，蛋白质的质量控制机制，通常在老化下降所需的纤毛结构的这种年龄依赖性的恢复。我们的研究结果提出了一种可能性，即在特定条件下可以绕过IFT基因中某些突变的影响，从而恢复纤毛功能。
The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT. We demonstrate that while DAF-16/FOXO is dispensable, the age-dependent suppression of cilia phenotypes in IFT mutants requires cell-autonomous functions of the HSF1 heat shock factor and the Hsp90 chaperone. Our results describe an unexpected role of early aging and protein quality control mechanisms in suppressing ciliary phenotypes of IFT mutants, and suggest possible strategies for targeting subsets of ciliopathies. Cilia are ‘antenna-like’ structures that are present on nearly all cell types in animals. These structures are important for sensing and signaling external cues to the cell. Most cilia are formed by a protein transport process called ‘intraflagellar transport’ or IFT. Mutations in IFT genes result in severe cilia defects, and are causal to a large number of diverse human disorders called ciliopathies. Since the genes and processes by which cilia are formed are similar across species, studies in experimental models such as the nematode C. elegans can greatly inform our overall understanding of cilia formation and function. Here we report the surprising observation that the structures and functions of severely defective cilia in nematodes with disrupted IFT genes markedly improve upon aging. We find that protein quality control mechanisms that normally decline in aging are required for this age-dependent recovery of cilia structure. Our results raise the possibility that the effects of some mutations in IFT genes can be bypassed under specific conditions, thereby restoring cilia functions.
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影响因子：
64.8
作者：
Barr, MM;Sternberg, PW
通讯作者：
Sternberg, PW
影响因子：
64.5
作者：
BARGMANN, CI;HARTWIEG, E;HORVITZ, HR
通讯作者：
HORVITZ, HR
影响因子：
16.6
作者：
Bizet AA;Becker-Heck A;Ryan R;Weber K;Filhol E;Krug P;Halbritter J;Delous M;Lasbennes MC;Linghu B;Oakeley EJ;Zarhrate M;Nitschké P;Garfa-Traore M;Serluca F;Yang F;Bouwmeester T;Pinson L;Cassuto E;Dubot P;Elshakhs NAS;Sahel JA;Salomon R;Drummond IA;Gubler MC;Antignac C;Chibout S;Szustakowski JD;Hildebrandt F;Lorentzen E;Sailer AW;Benmerah A;Saint-Mezard P;Saunier S
通讯作者：
Saunier S
影响因子：
5.4
作者：
Bitto A;Wang AM;Bennett CF;Kaeberlein M
通讯作者：
Kaeberlein M
影响因子：
7.7
作者：
Doroquez DB;Berciu C;Anderson JR;Sengupta P;Nicastro D
通讯作者：
Nicastro D