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Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Axonemal dynein assembly requires the R2TP complex component Pontin.
Development 2017 December 16
Pontin (Ruvbl1) and Reptin (Ruvbl2) are closely related AAA ATPases. They are components of the Ruvbl1-Ruvbl2-Tah1-Pih1 (R2TP) complexes that function as co-chaperones for the assembly of multiple macromolecular protein complexes. Here, we show that Pontin is essential for cilia motility in both zebrafish and mouse and that Pontin and Reptin function cooperatively in this process. Zebrafish pontin mutants display phenotypes tightly associated with cilia defects, and cilia motility is lost in a number of ciliated tissues along with a reduction in the number of outer and inner dynein arms. Pontin protein is enriched in cytosolic puncta in ciliated cells in zebrafish embryos. In mouse testis, Pontin is essential for the stabilization of axonemal dynein intermediate chain 1 (DNAI1) and DNAI2, the first appreciated step in axonemal dynein arm assembly. Strikingly, multiple dynein arm assembly factors show structural similarities to either Tah1 or Pih1, the other two components of the R2TP complex. Based on these results, we propose that Pontin and Reptin function to facilitate dynein arm assembly in cytosolic foci enriched with R2TP-like complexes.
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