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Publication : Broad-minded links cell cycle-related kinase to cilia assembly and hedgehog signal transduction.

First Author  Ko HW Year  2010
Journal  Dev Cell Volume  18
Issue  2 Pages  237-47
PubMed ID  20159594 Mgi Jnum  J:158583
Mgi Id  MGI:4439200 Doi  10.1016/j.devcel.2009.12.014
Citation  Ko HW, et al. (2010) Broad-minded links cell cycle-related kinase to cilia assembly and hedgehog signal transduction. Dev Cell 18(2):237-47
abstractText  Recent findings indicate that mammalian Sonic hedgehog (Shh) signal transduction occurs within primary cilia, although the cell biological mechanisms underlying both Shh signaling and ciliogenesis have not been fully elucidated. We show that an uncharacterized TBC domain-containing protein, Broad-minded (Bromi), is required for high-level Shh responses in the mouse neural tube. We find that Bromi controls ciliary morphology and proper Gli2 localization within the cilium. By use of a zebrafish model, we further show that Bromi is required for proper association between the ciliary membrane and axoneme. Bromi physically interacts with cell cycle-related kinase (CCRK), whose Chlamydomonas homolog regulates flagellar length. Biochemical and genetic interaction data indicate that Bromi promotes CCRK stability and function. We propose that Bromi and CCRK control the structure of the primary cilium by coordinating assembly of the axoneme and ciliary membrane, allowing Gli proteins to be properly activated in response to Shh signaling.
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