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Journal article
The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation
Nature genetics, v 43(1), pp 79-84
01 Jan 2011
PMID: 21131974
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with the abnormal function of motile cilia. Approximately half of individuals with PCD also have alterations in the left-right organization of their internal organ positioning, including situs inversus and situs ambiguous (Kartagener's syndrome). Here, we identify an uncharacterized coiled-coil domain containing a protein, CCDC40, essential for correct left-right patterning in mouse, zebrafish and human. In mouse and zebrafish, Ccdc40 is expressed in tissues that contain motile cilia, and mutations in Ccdc40 result in cilia with reduced ranges of motility. We further show that CCDC40 mutations in humans result in a variant of PCD characterized by misplacement of the central pair of microtubules and defective assembly of inner dynein arms and dynein regulatory complexes. CCDC40 localizes to motile cilia and the apical cytoplasm and is required for axonemal recruitment of CCDC39, disruption of which underlies a similar variant of PCD.
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Details
- Title
- The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation
- Creators
- Anita Becker-Heck - University Medical Center FreiburgIrene E. Zohn - Children's NationalNoriko Okabe - Princeton UniversityAndrew Pollock - Howard Hughes Medical InstituteKari Baker Lenhart - Princeton UniversityJessica Sullivan-Brown - Princeton UniversityJason McSheene - Princeton UniversityNiki T. Loges - University Medical Center FreiburgHeike Olbrich - Klinik und Poliklinik für Kinder- und JugendmedizinKarsten Haeffner - University Medical Center FreiburgManfred Fliegauf - University Medical Center FreiburgJudith Horvath - University Medical Center FreiburgRichard Reinhardt - Max Planck Institute for Plant Breeding ResearchKim G. Nielsen - Copenhagen University HospitalJune K. Marthin - Copenhagen University HospitalGyorgy Baktai - Pediatric Institute Svabhegy, Budapest, HungaryKathryn V. Anderson - Kettering UniversityRobert Geisler - Max Planck Institute for Developmental BiologyLee Niswander - Howard Hughes Medical InstituteHeymut Omran - University Medical Center FreiburgRebecca D. Burdine - Princeton University
- Publication Details
- Nature genetics, v 43(1), pp 79-84
- Publisher
- Springer Nature
- Number of pages
- 7
- Grant note
- R37HD035455 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Om 6/4; GRK1104; SFB592 / 'Deutsche Forschungsgemeinschaft' DFG; German Research Foundation (DFG) R37-HD035455 / Sloan-Kettering Institute Howard Hughes Medical Institute March of Dimes 01 KW9919 / German Human Genome Project DHGP R55HD035455 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) R01HD048584 / NICHD; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Spina Bifida Association R01NS044385 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000285683500020
- Scopus ID
- 2-s2.0-78651254549
- Other Identifier
- 991020111154704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Genetics & Heredity