IKKε Regulates Cell Elongation through Recycling Endosome Shuttling

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, IKK epsilon, regulates cytoskeletal organization and cell elongation. Here, we demonstrate that IKK epsilon 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. IKK epsilon regulates the localization of recycling endosonne regulators Rab11 and Dynein and phosphorylates their adaptor molecule, Nuclear fallout (Nuf). Nuf's negative regulation by IKK epsilon suggests that local activation of IKK epsilon 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.