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IKK-related kinases are key regulators of innate immunity and oncogenesis. While their effects on transcription are well characterized, their cytoplasmic functions remain poorly understood. Drosophila IKK-related kinase, IKKɛ, regulates cytoskeletal organization and cell elongation. Here, we demonstrate that IKKɛ is activated locally at the tip of growing mechanosensory bristles and regulates the rapid shuttling of recycling endosomes, independent of its roles in F-actin organization and caspase signaling. IKKɛ regulates the localization of recycling endosome regulators Rab11 and Dynein and phosphorylates their adaptor molecule, Nuclear fallout (Nuf). Nuf's negative regulation by IKKɛ suggests that local activation of IKKɛ inhibits Dynein on incoming recycling endosomes, converting them for outward transport. Mammalian IKK-related kinases also regulate the recycling endosomes' distribution by phosphorylating the Nuf homolog Rab11-FIP3. Our results establish an evolutionarily conserved function of IKK-related kinases in regulating recycling endosome dynamics and point to a key role of endosome dynamics in cell morphogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

Citation

Tetsuhisa Otani, Kenzi Oshima, Sachiko Onishi, Michiko Takeda, Kaori Shinmyozu, Shigenobu Yonemura, Shigeo Hayashi. IKKε regulates cell elongation through recycling endosome shuttling. Developmental cell. 2011 Feb 15;20(2):219-32

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PMID: 21316589

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