RRC ID 49273
Author Otani T, Oshima K, Onishi S, Takeda M, Shinmyozu K, Yonemura S, Hayashi S.
Title IKKε regulates cell elongation through recycling endosome shuttling.
Journal Dev Cell
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.
Volume 20(2)
Pages 219-32
Published 2011-2-15
DOI 10.1016/j.devcel.2011.02.001
PII S1534-5807(11)00046-3
PMID 21316589
MeSH Actins / metabolism Animal Structures / cytology Animal Structures / enzymology Animal Structures / growth & development Animal Structures / ultrastructure Animals Cell Membrane / metabolism Drosophila Proteins / metabolism Drosophila melanogaster / anatomy & histology Drosophila melanogaster / cytology* Drosophila melanogaster / enzymology* Dyneins / metabolism Endocytosis* Endosomes / metabolism* Endosomes / ultrastructure Enzyme Activation HEK293 Cells Humans I-kappa B Kinase / metabolism* Inhibitor of Apoptosis Proteins / metabolism Mice Mutation / genetics Nuclear Proteins / metabolism Phosphorylation Phosphoserine / metabolism Protein Binding Signal Transduction rab GTP-Binding Proteins / metabolism
IF 10.092
Times Cited 33
DNA material pUAST-IKKe-HA (RDB15214) pUAST-IKKe-myc (RDB15215) pUAST-IKKe[K41A]-HA (RDB15218) pCA-mIKKe-GFP (RDB15222) pCA-mIKKe-HA (RDB15223) pCA-mIKKe-Flag (RDB15224) pCA-hTBK1-GFP (RDB15225) pCA-hTBK1-HA (RDB15226) pCA-hTBK1-Flag (RDB15227).