Zhao, L., Yuan, S., Cao, Y., Kallakuri, S., Li, Y., Kishimoto, N., Dibella, L., and Sun, Z. (2013) Reptin/Ruvbl2 is a Lrrc6/Seahorse interactor essential for cilia motility. Proceedings of the National Academy of Sciences of the United States of America. 110(31):12697-702.
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 reptinhi2394 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 reptinhi2394 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.