-transparent.png){kind=logo}
CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation. 2014
Rim Hjeij, and
Alexandros Onoufriadis, and
Christopher M Watson, and
Christopher E Slagle, and
Nikolai T Klena, and
Gerard W Dougherty, and
Małgorzata Kurkowiak, and
Niki T Loges, and
Christine P Diggle, and
Nicholas F C Morante, and
George C Gabriel, and
Kristi L Lemke, and
You Li, and
Petra Pennekamp, and
Tabea Menchen, and
Franziska Konert, and
June Kehlet Marthin, and
Dorus A Mans, and
Stef J F Letteboer, and
Claudius Werner, and
Thomas Burgoyne, and
Cordula Westermann, and
Andrew Rutman, and
Ian M Carr, and
Christopher O'Callaghan, and
Eduardo Moya, and
Eddie M K Chung, and
, and
Eamonn Sheridan, and
Kim G Nielsen, and
Ronald Roepman, and
Kerstin Bartscherer, and
Rebecca D Burdine, and
Cecilia W Lo, and
Heymut Omran, and
Hannah M Mitchison
Department of General Pediatrics, University Children's Hospital Muenster, 48149 Muenster, Germany.
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.
Related Publications
Rim Hjeij, and
Alexandros Onoufriadis, and
Christopher M Watson, and
Christopher E Slagle, and
Nikolai T Klena, and
Gerard W Dougherty, and
Małgorzata Kurkowiak, and
Niki T Loges, and
Christine P Diggle, and
Nicholas F C Morante, and
George C Gabriel, and
Kristi L Lemke, and
You Li, and
Petra Pennekamp, and
Tabea Menchen, and
Franziska Konert, and
June Kehlet Marthin, and
Dorus A Mans, and
Stef J F Letteboer, and
Claudius Werner, and
Thomas Burgoyne, and
Cordula Westermann, and
Andrew Rutman, and
Ian M Carr, and
Christopher O'Callaghan, and
Eduardo Moya, and
Eddie M K Chung, and
, and
Eamonn Sheridan, and
Kim G Nielsen, and
Ronald Roepman, and
Kerstin Bartscherer, and
Rebecca D Burdine, and
Cecilia W Lo, and
Heymut Omran, and
Hannah M Mitchison
January 2013,
American journal of human genetics,
Rim Hjeij, and
Alexandros Onoufriadis, and
Christopher M Watson, and
Christopher E Slagle, and
Nikolai T Klena, and
Gerard W Dougherty, and
Małgorzata Kurkowiak, and
Niki T Loges, and
Christine P Diggle, and
Nicholas F C Morante, and
George C Gabriel, and
Kristi L Lemke, and
You Li, and
Petra Pennekamp, and
Tabea Menchen, and
Franziska Konert, and
June Kehlet Marthin, and
Dorus A Mans, and
Stef J F Letteboer, and
Claudius Werner, and
Thomas Burgoyne, and
Cordula Westermann, and
Andrew Rutman, and
Ian M Carr, and
Christopher O'Callaghan, and
Eduardo Moya, and
Eddie M K Chung, and
, and
Eamonn Sheridan, and
Kim G Nielsen, and
Ronald Roepman, and
Kerstin Bartscherer, and
Rebecca D Burdine, and
Cecilia W Lo, and
Heymut Omran, and
Hannah M Mitchison
November 2008,
American journal of human genetics,
Rim Hjeij, and
Alexandros Onoufriadis, and
Christopher M Watson, and
Christopher E Slagle, and
Nikolai T Klena, and
Gerard W Dougherty, and
Małgorzata Kurkowiak, and
Niki T Loges, and
Christine P Diggle, and
Nicholas F C Morante, and
George C Gabriel, and
Kristi L Lemke, and
You Li, and
Petra Pennekamp, and
Tabea Menchen, and
Franziska Konert, and
June Kehlet Marthin, and
Dorus A Mans, and
Stef J F Letteboer, and
Claudius Werner, and
Thomas Burgoyne, and
Cordula Westermann, and
Andrew Rutman, and
Ian M Carr, and
Christopher O'Callaghan, and
Eduardo Moya, and
Eddie M K Chung, and
, and
Eamonn Sheridan, and
Kim G Nielsen, and
Ronald Roepman, and
Kerstin Bartscherer, and
Rebecca D Burdine, and
Cecilia W Lo, and
Heymut Omran, and
Hannah M Mitchison
July 2006,
American journal of respiratory and critical care medicine,
Rim Hjeij, and
Alexandros Onoufriadis, and
Christopher M Watson, and
Christopher E Slagle, and
Nikolai T Klena, and
Gerard W Dougherty, and
Małgorzata Kurkowiak, and
Niki T Loges, and
Christine P Diggle, and
Nicholas F C Morante, and
George C Gabriel, and
Kristi L Lemke, and
You Li, and
Petra Pennekamp, and
Tabea Menchen, and
Franziska Konert, and
June Kehlet Marthin, and
Dorus A Mans, and
Stef J F Letteboer, and
Claudius Werner, and
Thomas Burgoyne, and
Cordula Westermann, and
Andrew Rutman, and
Ian M Carr, and
Christopher O'Callaghan, and
Eduardo Moya, and
Eddie M K Chung, and
, and
Eamonn Sheridan, and
Kim G Nielsen, and
Ronald Roepman, and
Kerstin Bartscherer, and
Rebecca D Burdine, and
Cecilia W Lo, and
Heymut Omran, and
Hannah M Mitchison
January 2017,
American journal of human genetics,
Rim Hjeij, and
Alexandros Onoufriadis, and
Christopher M Watson, and
Christopher E Slagle, and
Nikolai T Klena, and
Gerard W Dougherty, and
Małgorzata Kurkowiak, and
Niki T Loges, and
Christine P Diggle, and
Nicholas F C Morante, and
George C Gabriel, and
Kristi L Lemke, and
You Li, and
Petra Pennekamp, and
Tabea Menchen, and
Franziska Konert, and
June Kehlet Marthin, and
Dorus A Mans, and
Stef J F Letteboer, and
Claudius Werner, and
Thomas Burgoyne, and
Cordula Westermann, and
Andrew Rutman, and
Ian M Carr, and
Christopher O'Callaghan, and
Eduardo Moya, and
Eddie M K Chung, and
, and
Eamonn Sheridan, and
Kim G Nielsen, and
Ronald Roepman, and
Kerstin Bartscherer, and
Rebecca D Burdine, and
Cecilia W Lo, and
Heymut Omran, and
Hannah M Mitchison
May 2023,
Genetics in medicine : official journal of the American College of Medical Genetics,
Rim Hjeij, and
Alexandros Onoufriadis, and
Christopher M Watson, and
Christopher E Slagle, and
Nikolai T Klena, and
Gerard W Dougherty, and
Małgorzata Kurkowiak, and
Niki T Loges, and
Christine P Diggle, and
Nicholas F C Morante, and
George C Gabriel, and
Kristi L Lemke, and
You Li, and
Petra Pennekamp, and
Tabea Menchen, and
Franziska Konert, and
June Kehlet Marthin, and
Dorus A Mans, and
Stef J F Letteboer, and
Claudius Werner, and
Thomas Burgoyne, and
Cordula Westermann, and
Andrew Rutman, and
Ian M Carr, and
Christopher O'Callaghan, and
Eduardo Moya, and
Eddie M K Chung, and
, and
Eamonn Sheridan, and
Kim G Nielsen, and
Ronald Roepman, and
Kerstin Bartscherer, and
Rebecca D Burdine, and
Cecilia W Lo, and
Heymut Omran, and
Hannah M Mitchison
May 2012,
Nature genetics,
Rim Hjeij, and
Alexandros Onoufriadis, and
Christopher M Watson, and
Christopher E Slagle, and
Nikolai T Klena, and
Gerard W Dougherty, and
Małgorzata Kurkowiak, and
Niki T Loges, and
Christine P Diggle, and
Nicholas F C Morante, and
George C Gabriel, and
Kristi L Lemke, and
You Li, and
Petra Pennekamp, and
Tabea Menchen, and
Franziska Konert, and
June Kehlet Marthin, and
Dorus A Mans, and
Stef J F Letteboer, and
Claudius Werner, and
Thomas Burgoyne, and
Cordula Westermann, and
Andrew Rutman, and
Ian M Carr, and
Christopher O'Callaghan, and
Eduardo Moya, and
Eddie M K Chung, and
, and
Eamonn Sheridan, and
Kim G Nielsen, and
Ronald Roepman, and
Kerstin Bartscherer, and
Rebecca D Burdine, and
Cecilia W Lo, and
Heymut Omran, and
Hannah M Mitchison
December 2009,
American journal of human genetics,
Rim Hjeij, and
Alexandros Onoufriadis, and
Christopher M Watson, and
Christopher E Slagle, and
Nikolai T Klena, and
Gerard W Dougherty, and
Małgorzata Kurkowiak, and
Niki T Loges, and
Christine P Diggle, and
Nicholas F C Morante, and
George C Gabriel, and
Kristi L Lemke, and
You Li, and
Petra Pennekamp, and
Tabea Menchen, and
Franziska Konert, and
June Kehlet Marthin, and
Dorus A Mans, and
Stef J F Letteboer, and
Claudius Werner, and
Thomas Burgoyne, and
Cordula Westermann, and
Andrew Rutman, and
Ian M Carr, and
Christopher O'Callaghan, and
Eduardo Moya, and
Eddie M K Chung, and
, and
Eamonn Sheridan, and
Kim G Nielsen, and
Ronald Roepman, and
Kerstin Bartscherer, and
Rebecca D Burdine, and
Cecilia W Lo, and
Heymut Omran, and
Hannah M Mitchison
October 2013,
American journal of human genetics,
Rim Hjeij, and
Alexandros Onoufriadis, and
Christopher M Watson, and
Christopher E Slagle, and
Nikolai T Klena, and
Gerard W Dougherty, and
Małgorzata Kurkowiak, and
Niki T Loges, and
Christine P Diggle, and
Nicholas F C Morante, and
George C Gabriel, and
Kristi L Lemke, and
You Li, and
Petra Pennekamp, and
Tabea Menchen, and
Franziska Konert, and
June Kehlet Marthin, and
Dorus A Mans, and
Stef J F Letteboer, and
Claudius Werner, and
Thomas Burgoyne, and
Cordula Westermann, and
Andrew Rutman, and
Ian M Carr, and
Christopher O'Callaghan, and
Eduardo Moya, and
Eddie M K Chung, and
, and
Eamonn Sheridan, and
Kim G Nielsen, and
Ronald Roepman, and
Kerstin Bartscherer, and
Rebecca D Burdine, and
Cecilia W Lo, and
Heymut Omran, and
Hannah M Mitchison
January 2023,
Frontiers in genetics,
Rim Hjeij, and
Alexandros Onoufriadis, and
Christopher M Watson, and
Christopher E Slagle, and
Nikolai T Klena, and
Gerard W Dougherty, and
Małgorzata Kurkowiak, and
Niki T Loges, and
Christine P Diggle, and
Nicholas F C Morante, and
George C Gabriel, and
Kristi L Lemke, and
You Li, and
Petra Pennekamp, and
Tabea Menchen, and
Franziska Konert, and
June Kehlet Marthin, and
Dorus A Mans, and
Stef J F Letteboer, and
Claudius Werner, and
Thomas Burgoyne, and
Cordula Westermann, and
Andrew Rutman, and
Ian M Carr, and
Christopher O'Callaghan, and
Eduardo Moya, and
Eddie M K Chung, and
, and
Eamonn Sheridan, and
Kim G Nielsen, and
Ronald Roepman, and
Kerstin Bartscherer, and
Rebecca D Burdine, and
Cecilia W Lo, and
Heymut Omran, and
Hannah M Mitchison
November 2001,
American journal of respiratory cell and molecular biology,
