Transport of the outer dynein arm complex to cilia requires a cytoplasmic protein Lrrc6

Inaba, Yasuko; Shinohara, Kyosuke; Botilde, Yanick; Nabeshima, Ryo; Takaoka, Katsuyoshi; Ajima, Rieko; Lamri, Lynda; Takeda, Hiroyuki; Saga, Yumiko; Nakamura, Tetsuya; Hamada, Hiroshi

doi:10.1111/gtc.12380

Cited by 32 publications

(24 citation statements)

References 19 publications

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“…LRRC6/Seahorse (Leucine-Rich Repeat-Containing 6) ( Figure 2) is another DNAAFs whose defects cause primary ciliary dyskinesia (CILD19) [37][38][39]. LRRC6, containing several LRR repeats is another protein expressed specifically in cells with motile cilia, including the nodal, tracheal, and sperm cells in mice [39]. LRRC6, in addition to six LRR repeats at the N-terminus, also contains a CS domain at the C-terminus [48].…”

Section: Dnaafs and Their Function In Dynein Arm Assemblymentioning

confidence: 99%

“…The CS domain is likely essential for the direct interaction between LRRC6 and RuvBL2 [35,37,48] or DNAAF7 [35] (Table 1). In mutant mice and individuals affected with PCD lacking LRRC6 the length of cilia was normal, but nodal and typical motile cilia were immotile due to the loss of IDAs and ODAs [37][38][39] (Table 2). Probably, the lack of IDAs and ODAs in the axoneme of the mutant lacking LRRC6 was caused by defective transport of the dynein arm to the cilia [39].…”

Section: Dnaafs and Their Function In Dynein Arm Assemblymentioning

confidence: 99%

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Role of the Novel Hsp90 Co-Chaperones in Dynein Arms’ Preassembly

Fabczak

Osinka

2019

IJMS

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The outer and inner dynein arms (ODAs and IDAs) are composed of multiple subunits including dynein heavy chains possessing a motor domain. These complex structures are preassembled in the cytoplasm before being transported to the cilia. The molecular mechanism(s) controlling dynein arms’ preassembly is poorly understood. Recent evidence suggests that canonical R2TP complex, an Hsp-90 co-chaperone, in cooperation with dynein axonemal assembly factors (DNAAFs), plays a crucial role in the preassembly of ODAs and IDAs. Here, we have summarized recent data concerning the identification of novel chaperone complexes and their role in dynein arms’ preassembly and their association with primary cilia dyskinesia (PCD), a human genetic disorder.

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Section: Dnaafs and Their Function In Dynein Arm Assemblymentioning

confidence: 99%

Section: Dnaafs and Their Function In Dynein Arm Assemblymentioning

confidence: 99%

Role of the Novel Hsp90 Co-Chaperones in Dynein Arms’ Preassembly

Fabczak

Osinka

2019

IJMS

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“…High levels of homology between several DNAAFs (PIH1D3/DNAAF6, DNAAF2 and SPAG1) and key non-catalytic subunits (PIH1 and TAH1) of the well-known R2TP co-chaperone complex, further implicate these DNAAFs in chaperoning functions. Interactions between LRRC6, DNAAF1/LRRC50 and C21ORF59/Kurly were recently reported which, coupled with the phenotypic analysis of Lrrc6 mutant mice, suggests that these assembly factors may primarily function in apical targeting/trafficking of dynein complexes 9,10 . The functions of DNAAF5/HEATR2 which has no reported links to chaperones, remain elusive 11 .…”

Section: Introductionmentioning

confidence: 96%

ZMYND10 functions in a chaperone relay during axonemal dynein assembly

Mali

Yeyati

Mizuno

et al. 2017

Preprint

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“…In gene-targeted mice lacking functional LRRC6, cilia microtubules remained normal but the outer dynein arms (ODAs), the structures essential for the ciliary beating, are absent. In the absence of LRRC6, ODA proteins that normally are assembled in the cytoplasm and transported to the ciliary axoneme, remain in the cytoplasm and are not transported to the ciliary axoneme [ 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis comparing mouse strains with extreme total lung capacities identifies novel candidate genes for pulmonary function

et al. 2017

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BackgroundFailure to attain peak lung function by early adulthood is a risk factor for chronic lung diseases. Previously, we reported that C3H/HeJ mice have about twice total lung capacity (TLC) compared to JF1/MsJ mice. We identified seven lung function quantitative trait loci (QTL: Lfnq1-Lfnq7) in backcross/intercross mice derived from these inbred strains. We further demonstrated, superoxide dismutase 3, extracellular (Sod3), Kit oncogene (Kit) and secreted phosphoprotein 1 (Spp1) located on these Lfnqs as lung function determinants. Emanating from the concept of early origin of lung disease, we sought to identify novel candidate genes for pulmonary function by investigating lung transcriptome in C3H/HeJ and JF1/MsJ mice at the completion of embryonic development, bulk alveolar formation and maturity.MethodsDesign-based stereological analysis was performed to study lung structure in C3H/HeJ and JF1/MsJ mice. Microarray was used for lung transcriptomic analysis [embryonic day 18, postnatal days 28, 70]. Quantitative real time polymerase chain reaction (qRT-PCR), western blot and immunohistochemical analysis were used to confirm selected differences.ResultsStereological analysis revealed decreased alveolar number density, elastin to collagen ratio and increased mean alveolar volume in C3H/HeJ mice compared to JF1/MsJ. Gene ontology term “extracellular region” was enriched among the decreased JF1/MsJ transcripts. Candidate genes identified using the expression-QTL strategy include: ATP-binding cassette, sub-family G (WHITE), member 1 (Abcg1), formyl peptide receptor 1 (Fpr1), gamma-aminobutyric acid (GABA) B receptor, 1 (Gabbr1); histocompatibility 2 genes: class II antigen E beta (H2-Eb1), D region locus 1 (H2-D1), and Q region locus 4 (H2-Q4); leucine rich repeat containing 6 (testis) (Lrrc6), radial spoke head 1 homolog (Rsph1), and surfactant associated 2 (Sfta2). Noteworthy genes selected as candidates for their consistent expression include: Wnt inhibitor factor 1 (Wif1), follistatin (Fst), chitinase-like 1 (Chil1), and Chil3.ConclusionsComparison of late embryonic, adolescent and adult lung transcript profiles between mouse strains with extreme TLCs lead to the identification of candidate genes for pulmonary function that has not been reported earlier. Further mechanistic investigations are warranted to elucidate their mode of action in determining lung function.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-017-0629-3) contains supplementary material, which is available to authorized users.

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Transport of the outer dynein arm complex to cilia requires a cytoplasmic protein Lrrc6

Cited by 32 publications

References 19 publications

Role of the Novel Hsp90 Co-Chaperones in Dynein Arms’ Preassembly

Role of the Novel Hsp90 Co-Chaperones in Dynein Arms’ Preassembly

ZMYND10 functions in a chaperone relay during axonemal dynein assembly

Transcriptomic analysis comparing mouse strains with extreme total lung capacities identifies novel candidate genes for pulmonary function

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