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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Zhao, Lu Yuan, Shiaulou Li, Yuanyuan Kallakuri, Sowjanya Dibella, Linda Sun, Zhaoxia Cao, Ying Kishimoto, Norihito |
Description | Author Affiliation: Zhao L ( Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.); |
Abstract | Primary ciliary dyskinesia (PCD) is an autosomal recessive disease caused by defective cilia motility. The identified PCD genes account for about half of PCD incidences and the underlying mechanisms remain poorly understood. We demonstrate that Reptin/Ruvbl2, a protein known to be involved in epigenetic and transcriptional regulation, is essential for cilia motility in zebrafish. We further show that Reptin directly interacts with the PCD protein Lrrc6/Seahorse and this interaction is critical for the in vivo function of Lrrc6/Seahorse in zebrafish. Moreover, whereas the expression levels of multiple dynein arm components remain unchanged or become elevated, the density of axonemal dynein arms is reduced in reptin(hi2394) mutants. Furthermore, Reptin is highly enriched in the cytosol and colocalizes with Lrrc6/Seahorse. Combined, these results suggest that the Reptin-Lrrc6/Seahorse complex is involved in dynein arm formation. We also show that although the DNA damage response is induced in reptin(hi2394) mutants, it remains unchanged in cilia biogenesis mutants and lrrc6/seahorse mutants, suggesting that increased DNA damage response is not intrinsic to ciliary defects and that in vertebrate development, Reptin functions in multiple processes, both cilia specific and cilia independent. |
ISSN | 00278424 |
e-ISSN | 10916490 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Issue Number | 31 |
Volume Number | 110 |
Language | English |
Publisher | National Academy of Sciences |
Publisher Date | 2013-07-01 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | Axonemal Dyneins Metabolism Axoneme Nuclear Proteins Zebrafish Proteins Zebrafish Embryology Animals Genetics DNA Damage Mutation Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
Content Type | Text |
Resource Type | Article |
Subject | Multidisciplinary |
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