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秀丽隐杆线虫IFT突变体衰老过程中感觉纤毛的结构和功能恢复

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging.

作者信息

Cornils Astrid, Maurya Ashish K, Tereshko Lauren, Kennedy Julie, Brear Andrea G, Prahlad Veena, Blacque Oliver E, Sengupta Piali

机构信息

Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts.

School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.

出版信息

PLoS Genet. 2016 Dec 1;12(12):e1006325. doi: 10.1371/journal.pgen.1006325. eCollection 2016 Dec.

Abstract

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.

摘要

大多数纤毛是通过高度保守的鞭毛内运输(IFT)过程形成和维持的。IFT基因的突变会导致纤毛结构缺陷和称为纤毛病的全身性疾病。在这里,我们表明,秀丽隐杆线虫中低表达IFT突变体的严重截断的感觉纤毛在成年衰老的离散时期会短暂延长,从而导致感觉行为明显改善。纤毛形态的年龄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DAF-16/FOXO是可有可无的,但IFT突变体中纤毛表型的年龄依赖性抑制需要HSF1热休克因子和Hsp90伴侣的细胞自主功能。我们的结果描述了衰老早期和蛋白质质量控制机制在抑制IFT突变体纤毛表型中的意外作用,并提出了针对纤毛病亚群的可能策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9885/5131903/c7d3c69ba035/pgen.1006325.g001.jpg

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