title: Transport of the outer dynein arm complex to cilia requires a cytoplasmic protein Lrrc6.
abstract: 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.
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Inaba
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Shinohara
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yanick
authors.initials: Y
authors.lastname: Botilde
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nabeshima
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Takaoka
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Ajima
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Lynda
authors.initials: L
authors.lastname: Lamri
authors.affiliation: Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Yata 1111, Mishima, Shizuoka, 411-8540, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
mesh_terms: D000818:Animals; D056444:Axonemal Dyneins / Q000235:genetics; D054468:Axoneme / Q000235:genetics / Q000473:pathology; D002923:Cilia / Q000235:genetics* / Q000473:pathology; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004195:Disease Models, Animal; D004398:Dyneins / Q000235:genetics; D006801:Humans; D007619:Kartagener Syndrome / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011506:Proteins / Q000235:genetics*
chemical_list: D003598:Cytoskeletal Proteins; C411573:Lrrc6 protein, mouse; D011506:Proteins; D056444:Axonemal Dyneins; C497507:DNAH5 protein, human; C430745:DNAH9 protein, human; D004398:Dyneins