Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.
Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.
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DOI：
10.1016/j.devcel.2017.11.014
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发表时间：
2017-12-18
影响因子：
11.8
通讯作者：
Reiter JF
中科院分区：
文献类型：
--
作者：
Sigg MA;Menchen T;Lee C;Johnson J;Jungnickel MK;Choksi SP;Garcia G 3rd;Busengdal H;Dougherty GW;Pennekamp P;Werner C;Rentzsch F;Florman HM;Krogan N;Wallingford JB;Omran H;Reiter JF
纤毛是专门用于运动和信号的细胞器。为了推断在进化过程中的信号通路成为与纤毛，我们的特点是从海胆，海葵和choanoflagellates纤毛的蛋白质组。我们鉴定了437个在哺乳动物中保守的高置信度纤毛候选蛋白，并发现Hh和GPCR途径在动物起源之前与双动脉起源和TRP通道起源之前与纤毛相关。我们证明，候选人没有以前参与纤毛生物学定位到纤毛，并进一步研究ENKUR，TRP通道相互作用蛋白在所有三种生物体的纤毛。ENKUR定位于运动纤毛，是脊椎动物左/右轴图案化所必需的。此外，ENKUR的突变会导致人类内脏逆位。因此，从不同的真核生物纤毛蛋白质组学分析定义了一个保守的纤毛蛋白质组，揭示了古老的连接信号，并揭示了纤毛蛋白，控制发展和人类疾病。纤毛是用于运动和细胞间通讯的细胞附属物。通过海胆、海葵和领鞭毛虫纤毛的蛋白质组学重建纤毛的进化祖先。一种已鉴定的纤毛蛋白ENKUR有助于脊椎动物左/右身体轴的模式。具有ENKUR遗传突变的人类具有内脏逆位。
Cilia are organelles specialized for movement and signaling. To infer when during evolution signaling pathways became associated with cilia, we characterized the proteomes of cilia from sea urchins, sea anemones and choanoflagellates. We identified 437 high confidence ciliary candidate proteins conserved in mammals and discovered that Hh and GPCR pathways were linked to cilia before the origin of bilateria and TRP channels before the origin of animals. We demonstrated that candidates not previously implicated in ciliary biology localized to cilia and further investigated ENKUR, a TRP channel-interacting protein identified in the cilia of all three organisms. ENKUR localizes to motile cilia and is required for patterning the left/right axis in vertebrates. Moreover, mutation of ENKUR causes situs inversus in humans. Thus, proteomic profiling of cilia from diverse eukaryotes defines a conserved ciliary proteome, reveals ancient connections to signaling, and uncovers a ciliary protein that controls development and human disease. Cilia are cellular appendages used for motility and intercellular communication. Sigg et al. reconstruct the evolutionary ancestry of cilia through proteomics of sea urchin, sea anemone, and choanoflagellate cilia. One identified ciliary protein, ENKUR, helps pattern the vertebrate left/right body axis. Humans with inherited mutations in ENKUR have situs inversus.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7.4
作者：
Clauser, KR;Baker, P;Burlingame, AL
通讯作者：
Burlingame, AL
影响因子：
--
作者：
Boesger, Jens;Wagner, Volker;Mittag, Maria
通讯作者：
Mittag, Maria
DOI：
10.1164/rccm.200406-710st
发表时间：
2005-04-15
影响因子：
24.7
作者：
American Thoracic Society;European Respiratory Society
通讯作者：
European Respiratory Society
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR