ENKD1 is a centrosomal and ciliary microtubule‐associated protein important for primary cilium content regulation
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...
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Veröffentlicht in: | The FEBS journal 2022-07, Vol.289 (13), p.3789-3812 |
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Sprache: | eng |
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Zusammenfassung: | 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.
Primary cilium acts as a signaling center for developmentally important signaling pathways. Its deregulation causes multisystemic developmental disorders. We identified the Enkurin domain containing 1 (ENKD1) as a microtubule‐associated protein that localizes to the centrosomes and the primary cilium. Depletion of ENKD1 in cells results in shorter cilia, reduced ciliary concentration of IFT‐B component IFT88, increased ciliary concentration of small GTPase, Arl13b and defective Hedgehog signaling. |
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ISSN: | 1742-464X 1742-4658 |
DOI: | 10.1111/febs.16367 |