IKKɛ Regulates Cell Elongation through Recycling Endosome Shuttling

SummaryIKK-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.

Graphical AbstractFigure optionsDownload high-quality image (411 K)Download as PowerPoint slideHighlights
► Recycling endosomes shuttle along the proximal-distal axis of growing bristles
► IKKɛ locally antagonizes Rab11 effector Nuf at the bristle tip by phosphorylation
► Nuf-endosome pathway is independent of actin cytoskeleton or DIAP1-caspase pathway
► Mammalian IKK-related kinases antagonize Rab11-FIP3 through phosphorylation