DYX1C1 is required for axonemal dynein assembly and ciliary motility.
DYX1C1 is required for axonemal dynein assembly and ciliary motility.
复制标题
DOI：
10.1038/ng.2707
复制
发表时间：
2013-09
期刊：
影响因子：
30.8
通讯作者：
Omran, Heymut
中科院分区：
文献类型：
--
作者：
Tarkar, Aarti;Loges, Niki T.;Slagle, Christopher E.;Francis, Richard;Dougherty, Gerard W.;Tamayo, Joel V.;Shook, Brett;Cantino, Marie;Schwartz, Daniel;Jahnke, Charlotte;Olbrich, Heike;Werner, Claudius;Raidt, Johanna;Pennekamp, Petra;Abouhamed, Marouan;Hjeij, Rim;Koehler, Gabriele;Griese, Matthias;Li, You;Lemke, Kristi;Klena, Nikolas;Liu, Xiaoqin;Gabriel, George;Tobita, Kimimasa;Jaspers, Martine;Morgan, Lucy C.;Shapiro, Adam J.;Letteboer, Stef J. F.;Mans, Dorus A.;Carson, Johnny L.;Leigh, Margaret W.;Wolf, Whitney E.;Chen, Serafine;Lucas, Jane S.;Onoufriadis, Alexandros;Plagnol, Vincent;Schmidts, Miriam;Boldt, Karsten;Roepman, Ronald;Zariwala, Maimoona A.;Lo, Cecilia W.;Mitchison, Hannah M.;Knowles, Michael R.;Burdine, Rebecca D.;LoTurco, Joseph J.;Omran, Heymut
Dyx1c1与阅读障碍和发育中的新皮质神经元迁移有关。出乎意料的是，我们在小鼠中发现Dyx1c1外显子2-4的缺失导致了类似于原发性睫状肌运动障碍(PCD)的表型，PCD是一种以慢性呼吸道疾病、偏侧缺陷和男性不育为特征的遗传异质性疾病。在ENU突变筛选中发现Dyx1c1c.T2a起始密码子突变的小鼠中，这种表型得到了独立的证实。针对斑马鱼dyx1c1的Morpholinos也造成了偏侧性和纤毛运动缺陷。在人类中，在12名PCD患者中发现了隐性功能丧失的DYX1C1突变。对小鼠和人的DYX1C1突变的运动纤毛进行了超微结构和免疫荧光分析，发现外臂和内臂动力蛋白(oda/ida)断裂。DYX1c1定位于呼吸道上皮细胞的胞浆，其相互作用体富含分子伴侣，并与胞质内的oda/IDA组装因子DNAAF2/KTU相互作用。因此，我们认为DYX1C1是一个新发现的动力蛋白轴丝组装因子(DNAAF4)。
Dyx1c1 has been associated with dyslexia and neuronal migration in the developing neocortex. Unexpectedly, we found that deletion of Dyx1c1 exons 2–4 in mice caused a phenotype resembling primary ciliary dyskinesia (PCD), a genetically heterogeneous disorder characterized by chronic airway disease, laterality defects, and male infertility. This phenotype was confirmed independently in mice with a Dyx1c1c.T2A start codon mutation recovered from an ENU mutagenesis screen. Morpholinos targeting dyx1c1 in zebrafish also created laterality and ciliary motility defects. In humans, recessive loss-of-function DYX1C1 mutations were identified in twelve PCD individuals. Ultrastructural and immunofluorescence analyses of DYX1C1-mutant motile cilia in mice and humans revealed disruptions of outer and inner dynein arms (ODA/IDA). DYX1C1 localizes to the cytoplasm of respiratory epithelial cells, its interactome is enriched for molecular chaperones, and it interacts with the cytoplasmic ODA/IDA assembly factor DNAAF2/KTU. Thus, we propose that DYX1C1 is a newly identified dynein axonemal assembly factor (DNAAF4).
登录
查看更多内容
影响因子：
2.1
作者：
Hatakeyama, S;Matsumoto, M;Nakayama, KI
通讯作者：
Nakayama, KI
影响因子：
5.2
作者：
Marino, C;Giorda, R;Molteni, M
通讯作者：
Molteni, M
影响因子：
9.8
作者：
Loges, Niki Tomas;Olbrich, Heike;Omran, Heymut
通讯作者：
Omran, Heymut
影响因子：
9.8
作者：
Kott, Esther;Duquesnoy, Philippe;Amselem, Serge
通讯作者：
Amselem, Serge
影响因子：
30.8
作者：
通讯作者：
--