Transport of the outer dynein arm complex to cilia requires a cytoplasmic protein Lrrc6
Transport of the outer dynein arm complex to cilia requires a cytoplasmic protein Lrrc6
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DOI：
10.1111/gtc.12380
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发表时间：
2016-07-01
期刊：
影响因子：
2.1
通讯作者：
Hamada, Hiroshi
中科院分区：
文献类型：
--
作者：
Inaba, Yasuko;Shinohara, Kyosuke;Hamada, Hiroshi
Lrrc6编码一种细胞质蛋白，该蛋白在具有运动纤毛的细胞中特异表达，包括小鼠的结节、气管和睾丸。在原发性睫状体运动障碍(PCD)患者中发现了Lrrc6突变。缺乏Lrrc6的突变小鼠表现出典型的PCD缺陷，如脑积水和偏侧缺陷。我们发现，在没有Lrrc6的情况下，运动纤毛的形态保持正常，但其运动完全丧失。在Lrrc6(-/-)小鼠，微管的9+2排列仍然正常，但纤毛中缺少纤毛搏动所必需的外动力蛋白臂(ODAS)。在没有Lrrc6的情况下，DNAH5、DNAH9和IC2等在细胞质中组装并运输到纤毛轴丝的oda蛋白留在细胞质中，而不运输到纤毛轴丝。IC2-IC1相互作用是oda组装的第一步，在Lrrc6(-/-)小鼠睾丸中是正常的。我们的结果表明，oda蛋白可能通过Lrrc6依赖的机制从细胞质运输到纤毛。
Lrrc6 encodes a cytoplasmic protein that is expressed specifically in cells with motile cilia including the node, trachea and testes of the mice. A mutation of Lrrc6 has been identified in human patients with primary ciliary dyskinesia (PCD). Mutant mice lacking Lrrc6 show typical PCD defects such as hydrocephalus and laterality defects. We found that in the absence of Lrrc6, the morphology of motile cilia remained normal, but their motility was completely lost. The 9+2 arrangement of microtubules remained normal in Lrrc6(-/-) mice, but the outer dynein arms (ODAs), the structures essential for the ciliary beating, were absent from the cilia. In the absence of Lrrc6, ODA proteins such as DNAH5, DNAH9 and IC2, which are assembled in the cytoplasm and transported to the ciliary axoneme, remained in the cytoplasm and were not transported to the ciliary axoneme. The IC2-IC1 interaction, which is the first step of ODA assembly, was normal in Lrrc6(-/-) mice testes. Our results suggest that ODA proteins may be transported from the cytoplasm to the cilia by an Lrrc6-dependent mechanism.