title: IKKε regulates cell elongation through recycling endosome shuttling.
abstract: 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.
authors.affiliation: Laboratory for Morphogenetic Signaling, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
authors.forename: Tetsuhisa
authors.initials: T
authors.lastname: Otani
authors.forename: Kenzi
authors.initials: K
authors.lastname: Oshima
authors.forename: Sachiko
authors.initials: S
authors.lastname: Onishi
authors.forename: Michiko
authors.initials: M
authors.lastname: Takeda
authors.forename: Kaori
authors.initials: K
authors.lastname: Shinmyozu
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Hayashi
mesh_terms: D000199:Actins / Q000378:metabolism; D000825:Animal Structures / Q000166:cytology / Q000201:enzymology / Q000254:growth & development / Q000648:ultrastructure; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000166:cytology* / Q000201:enzymology*; D004398:Dyneins / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D004789:Enzyme Activation; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D004398:Dyneins; D051550:I-kappa B Kinase; D051034:Inhibitor of Apoptosis Proteins; D009687:Nuclear Proteins; D010768:Phosphoserine; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C111891:DIAP1 protein, Drosophila; C111662:nuf protein, Drosophila