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ENKD1 is a centrosomal and ciliary microtubule-associated protein important for primary cilium content regulation.

Fatmanur TiryakiJovana DereticElif Nur Firat Karalar
Published in: The FEBS journal (2022)
Centrioles and cilia are conserved, microtubule-based structures critical for cell function and development. Their dysfunction causes cancer and developmental disorders. How microtubules are organized into ordered structures by microtubule-associated proteins (MAPs) and tubulin modifications is best understood during mitosis but is largely unexplored for the centrioles and the ciliary axoneme, which are composed of stable microtubules that maintain their length at a steady-state. In particular, we know little about the identity of the centriolar and ciliary MAPs and how they work together during the assembly and maintenance of the cilium and centriole. Here, we identified the Enkurin domain containing 1 (ENKD1) as a component of the centriole wall and the axoneme in mammalian cells and showed that it has extensive proximity interactions with these compartments and MAPs. Using in vitro and cellular assays, we found that ENKD1 is a new MAP that regulates microtubule organization and stability. Consistently, we observed an increase in tubulin polymerization and microtubule stability, as well as disrupted microtubule organization in ENKD1 overexpression. Cells depleted for ENKD1 were defective in ciliary length and content regulation and failed to respond to Hedgehog pathway activation. Together, our results advance our understanding of the functional and regulatory relationship between MAPs and the primary cilium.
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