Cby1 promotes Ahi1 recruitment to a ring-shaped domain at the centriole-cilium interface and facilitates proper cilium formation and function.
Bottom Line: Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies.Superresolution microscopy using both three-dimensional SIM and STED reveals that Cby1 localizes to an ∼250-nm ring at the distal end of the mature centriole, in close proximity to Ofd1 and Ahi1, a component of the transition zone between centriole and cilium.This suggests that Cby1 is required for efficient recruitment of Ahi1, providing a possible molecular mechanism for the ciliogenesis defect in Cby1(-/-) cells.
Affiliation: Department of Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94305.Show MeSH
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Mentions: We showed that deletion of Cby1 results in reduced efficiency of primary cilium formation in culture and in cystic kidneys, a cilium-associated defect, in vivo. A possible molecular basis for these effects was revealed by our finding that Cby1 is required for full recruitment of Arl13b to the primary cilium, suggesting a role in determining ciliary protein content. In addition, we showed that the Cby1 protein localizes to a specific compartment at the distal end of the centriole with Ofd1 and Ahi1 and is important for the function of the transition zone between centriole and cilium. The function of Cby1 may be mediated in part by Ahi1, which is reduced at the centrosome of Cby1−/− cells. Given the known functions of these proteins in cilium structure and function (Hsiao et al., 2009; Singla et al., 2010; Lancaster et al., 2011), we propose that the defect in determining ciliary protein content in Cby1−/− cells is due to functional disruption of this domain. We summarize these findings in a model in Figure 8.
Affiliation: Department of Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94305.