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CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation

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Harvard

Hjeij, R, Onoufriadis, A, Watson, CM, Slagle, CE, Klena, NT, Dougherty, GW, Kurkowiak, M, Loges, NT, Diggle, CP, Morante, NFC, Gabriel, GC, Lemke, KL, Li, Y, Pennekamp, P, Menchen, T, Konert, F, Marthin, JK, Mans, DA, Letteboer, SJF, Werner, C, Burgoyne, T, Westermann, C, Rutman, A, Carr, IM, O'Callaghan, C, Moya, E, Chung, EMK, Sheridan, E, Nielsen, KG, Roepman, R, Bartscherer, K, Burdine, RD, Lo, CW, Omran, H, Mitchison, HM & UK10K Consortium 2014, 'CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation' American Journal of Human Genetics, bind 95, nr. 3, s. 257-74. https://doi.org/10.1016/j.ajhg.2014.08.005

APA

Hjeij, R., Onoufriadis, A., Watson, C. M., Slagle, C. E., Klena, N. T., Dougherty, G. W., ... UK10K Consortium (2014). CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation. American Journal of Human Genetics, 95(3), 257-74. https://doi.org/10.1016/j.ajhg.2014.08.005

CBE

Hjeij R, Onoufriadis A, Watson CM, Slagle CE, Klena NT, Dougherty GW, Kurkowiak M, Loges NT, Diggle CP, Morante NFC, Gabriel GC, Lemke KL, Li Y, Pennekamp P, Menchen T, Konert F, Marthin JK, Mans DA, Letteboer SJF, Werner C, Burgoyne T, Westermann C, Rutman A, Carr IM, O'Callaghan C, Moya E, Chung EMK, Sheridan E, Nielsen KG, Roepman R, Bartscherer K, Burdine RD, Lo CW, Omran H, Mitchison HM, UK10K Consortium. 2014. CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation. American Journal of Human Genetics. 95(3):257-74. https://doi.org/10.1016/j.ajhg.2014.08.005

MLA

Vancouver

Author

Hjeij, Rim ; Onoufriadis, Alexandros ; Watson, Christopher M ; Slagle, Christopher E ; Klena, Nikolai T ; Dougherty, Gerard W ; Kurkowiak, Małgorzata ; Loges, Niki T ; Diggle, Christine P ; Morante, Nicholas F C ; Gabriel, George C ; Lemke, Kristi L ; Li, You ; Pennekamp, Petra ; Menchen, Tabea ; Konert, Franziska ; Marthin, June Kehlet ; Mans, Dorus A ; Letteboer, Stef J F ; Werner, Claudius ; Burgoyne, Thomas ; Westermann, Cordula ; Rutman, Andrew ; Carr, Ian M ; O'Callaghan, Christopher ; Moya, Eduardo ; Chung, Eddie M K ; Sheridan, Eamonn ; Nielsen, Kim G ; Roepman, Ronald ; Bartscherer, Kerstin ; Burdine, Rebecca D ; Lo, Cecilia W ; Omran, Heymut ; Mitchison, Hannah M ; UK10K Consortium. / CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation. I: American Journal of Human Genetics. 2014 ; Bind 95, Nr. 3. s. 257-74.

Bibtex

@article{6c32579bf0b14f9aadae455dead1be14,
title = "CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation",
abstract = "A diverse family of cytoskeletal dynein motors powers various cellular transport systems, including axonemal dyneins generating the force for ciliary and flagellar beating essential to movement of extracellular fluids and of cells through fluid. Multisubunit outer dynein arm (ODA) motor complexes, produced and preassembled in the cytosol, are transported to the ciliary or flagellar compartment and anchored into the axonemal microtubular scaffold via the ODA docking complex (ODA-DC) system. In humans, defects in ODA assembly are the major cause of primary ciliary dyskinesia (PCD), an inherited disorder of ciliary and flagellar dysmotility characterized by chronic upper and lower respiratory infections and defects in laterality. Here, by combined high-throughput mapping and sequencing, we identified CCDC151 loss-of-function mutations in five affected individuals from three independent families whose cilia showed a complete loss of ODAs and severely impaired ciliary beating. Consistent with the laterality defects observed in these individuals, we found Ccdc151 expressed in vertebrate left-right organizers. Homozygous zebrafish ccdc151(ts272a) and mouse Ccdc151(Snbl) mutants display a spectrum of situs defects associated with complex heart defects. We demonstrate that CCDC151 encodes an axonemal coiled coil protein, mutations in which abolish assembly of CCDC151 into respiratory cilia and cause a failure in axonemal assembly of the ODA component DNAH5 and the ODA-DC-associated components CCDC114 and ARMC4. CCDC151-deficient zebrafish, planaria, and mice also display ciliary dysmotility accompanied by ODA loss. Furthermore, CCDC151 coimmunoprecipitates CCDC114 and thus appears to be a highly evolutionarily conserved ODA-DC-related protein involved in mediating assembly of both ODAs and their axonemal docking machinery onto ciliary microtubules.",
keywords = "Animals, Axonemal Dyneins, Axoneme, Cells, Cultured, Cilia, Embryo, Mammalian, Exome, Female, Fluorescent Antibody Technique, Humans, Immunoblotting, Immunoprecipitation, In Situ Hybridization, Kartagener Syndrome, Male, Mice, Mice, Knockout, Microtubule-Associated Proteins, Mutation, Pedigree, Phenotype, Two-Hybrid System Techniques, Zebrafish",
author = "Rim Hjeij and Alexandros Onoufriadis and Watson, {Christopher M} and Slagle, {Christopher E} and Klena, {Nikolai T} and Dougherty, {Gerard W} and Małgorzata Kurkowiak and Loges, {Niki T} and Diggle, {Christine P} and Morante, {Nicholas F C} and Gabriel, {George C} and Lemke, {Kristi L} and You Li and Petra Pennekamp and Tabea Menchen and Franziska Konert and Marthin, {June Kehlet} and Mans, {Dorus A} and Letteboer, {Stef J F} and Claudius Werner and Thomas Burgoyne and Cordula Westermann and Andrew Rutman and Carr, {Ian M} and Christopher O'Callaghan and Eduardo Moya and Chung, {Eddie M K} and Eamonn Sheridan and Nielsen, {Kim G} and Ronald Roepman and Kerstin Bartscherer and Burdine, {Rebecca D} and Lo, {Cecilia W} and Heymut Omran and Mitchison, {Hannah M} and {UK10K Consortium}",
note = "Copyright {\circledC} 2014 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2014",
month = "9",
day = "4",
doi = "10.1016/j.ajhg.2014.08.005",
language = "English",
volume = "95",
pages = "257--74",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation

AU - Hjeij, Rim

AU - Onoufriadis, Alexandros

AU - Watson, Christopher M

AU - Slagle, Christopher E

AU - Klena, Nikolai T

AU - Dougherty, Gerard W

AU - Kurkowiak, Małgorzata

AU - Loges, Niki T

AU - Diggle, Christine P

AU - Morante, Nicholas F C

AU - Gabriel, George C

AU - Lemke, Kristi L

AU - Li, You

AU - Pennekamp, Petra

AU - Menchen, Tabea

AU - Konert, Franziska

AU - Marthin, June Kehlet

AU - Mans, Dorus A

AU - Letteboer, Stef J F

AU - Werner, Claudius

AU - Burgoyne, Thomas

AU - Westermann, Cordula

AU - Rutman, Andrew

AU - Carr, Ian M

AU - O'Callaghan, Christopher

AU - Moya, Eduardo

AU - Chung, Eddie M K

AU - Sheridan, Eamonn

AU - Nielsen, Kim G

AU - Roepman, Ronald

AU - Bartscherer, Kerstin

AU - Burdine, Rebecca D

AU - Lo, Cecilia W

AU - Omran, Heymut

AU - Mitchison, Hannah M

AU - UK10K Consortium

N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2014/9/4

Y1 - 2014/9/4

N2 - A diverse family of cytoskeletal dynein motors powers various cellular transport systems, including axonemal dyneins generating the force for ciliary and flagellar beating essential to movement of extracellular fluids and of cells through fluid. Multisubunit outer dynein arm (ODA) motor complexes, produced and preassembled in the cytosol, are transported to the ciliary or flagellar compartment and anchored into the axonemal microtubular scaffold via the ODA docking complex (ODA-DC) system. In humans, defects in ODA assembly are the major cause of primary ciliary dyskinesia (PCD), an inherited disorder of ciliary and flagellar dysmotility characterized by chronic upper and lower respiratory infections and defects in laterality. Here, by combined high-throughput mapping and sequencing, we identified CCDC151 loss-of-function mutations in five affected individuals from three independent families whose cilia showed a complete loss of ODAs and severely impaired ciliary beating. Consistent with the laterality defects observed in these individuals, we found Ccdc151 expressed in vertebrate left-right organizers. Homozygous zebrafish ccdc151(ts272a) and mouse Ccdc151(Snbl) mutants display a spectrum of situs defects associated with complex heart defects. We demonstrate that CCDC151 encodes an axonemal coiled coil protein, mutations in which abolish assembly of CCDC151 into respiratory cilia and cause a failure in axonemal assembly of the ODA component DNAH5 and the ODA-DC-associated components CCDC114 and ARMC4. CCDC151-deficient zebrafish, planaria, and mice also display ciliary dysmotility accompanied by ODA loss. Furthermore, CCDC151 coimmunoprecipitates CCDC114 and thus appears to be a highly evolutionarily conserved ODA-DC-related protein involved in mediating assembly of both ODAs and their axonemal docking machinery onto ciliary microtubules.

AB - A diverse family of cytoskeletal dynein motors powers various cellular transport systems, including axonemal dyneins generating the force for ciliary and flagellar beating essential to movement of extracellular fluids and of cells through fluid. Multisubunit outer dynein arm (ODA) motor complexes, produced and preassembled in the cytosol, are transported to the ciliary or flagellar compartment and anchored into the axonemal microtubular scaffold via the ODA docking complex (ODA-DC) system. In humans, defects in ODA assembly are the major cause of primary ciliary dyskinesia (PCD), an inherited disorder of ciliary and flagellar dysmotility characterized by chronic upper and lower respiratory infections and defects in laterality. Here, by combined high-throughput mapping and sequencing, we identified CCDC151 loss-of-function mutations in five affected individuals from three independent families whose cilia showed a complete loss of ODAs and severely impaired ciliary beating. Consistent with the laterality defects observed in these individuals, we found Ccdc151 expressed in vertebrate left-right organizers. Homozygous zebrafish ccdc151(ts272a) and mouse Ccdc151(Snbl) mutants display a spectrum of situs defects associated with complex heart defects. We demonstrate that CCDC151 encodes an axonemal coiled coil protein, mutations in which abolish assembly of CCDC151 into respiratory cilia and cause a failure in axonemal assembly of the ODA component DNAH5 and the ODA-DC-associated components CCDC114 and ARMC4. CCDC151-deficient zebrafish, planaria, and mice also display ciliary dysmotility accompanied by ODA loss. Furthermore, CCDC151 coimmunoprecipitates CCDC114 and thus appears to be a highly evolutionarily conserved ODA-DC-related protein involved in mediating assembly of both ODAs and their axonemal docking machinery onto ciliary microtubules.

KW - Animals

KW - Axonemal Dyneins

KW - Axoneme

KW - Cells, Cultured

KW - Cilia

KW - Embryo, Mammalian

KW - Exome

KW - Female

KW - Fluorescent Antibody Technique

KW - Humans

KW - Immunoblotting

KW - Immunoprecipitation

KW - In Situ Hybridization

KW - Kartagener Syndrome

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Microtubule-Associated Proteins

KW - Mutation

KW - Pedigree

KW - Phenotype

KW - Two-Hybrid System Techniques

KW - Zebrafish

U2 - 10.1016/j.ajhg.2014.08.005

DO - 10.1016/j.ajhg.2014.08.005

M3 - Journal article

VL - 95

SP - 257

EP - 274

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 3

ER -

ID: 45096404