期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 93, 期 2, 页码 336-345出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2013.06.007
关键词
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资金
- National Institutes of Health (NIH) [DK068306, DK090917, DK091405, DK053093, DK070263, EY013408, DK092808-01A1, 5 U54 HL096458-06]
- NIH from the National Center for Advancing Translational Sciences [UL1 TR000083, UL1 TR000154]
- project Studies of nucleic acids and proteins from basic to applied research
- Foundation for Polish Science
- European Union Regional Development Fund
- Department of Pathology, Faculty of Medicine, Kuwait University
- Office of the Director
- Office of Rare Diseases Research
- National Heart, Lung, and Blood Institute (NHLBI)
- NIH NHLBI [5 R01HL071798]
- Deutsche Forschungsgemeinschaft [DFG Om 6/4, Om 6/5, GRK1104, SFB592]
- IZKF Munster
- Cell Dynamics and Disease graduate school
- project SYSCILIA from the European Community
Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function.
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