title: Serum- and Glucocorticoid-Inducible Kinase-1 (SGK-1) Plays a Role in Membrane Trafficking in Caenorhabditis elegans.
abstract: The mammalian serum- and glucocorticoid-inducible kinase SGK1 regulates the endocytosis of ion channels. Here we report that in C. elegans sgk-1 null mutants, GFP-tagged MIG-14/Wntless, the sorting receptor of Wnt, failed to localize to the basolateral membrane of intestinal cells; instead, it was mis-sorted to lysosomes. This effect can be explained in part by altered sphingolipid levels, because reducing glucosylceramide biosynthesis restored the localization of MIG-14::GFP. Membrane traffic was not perturbed in general, as no obvious morphological defects were detected for early endosomes, the Golgi apparatus, and the endoplasmic reticulum (ER) in sgk-1 null animals. The recycling of MIG-14/Wntless through the Golgi might be partially responsible for the observed phenotype because the subcellular distribution of two plasma membrane cargoes that do not recycle through the trans-Golgi network (TGN) was affected to a lesser degree. Consistently, knockdown of the ArfGEF gbf-1 altered the distribution of SGK-1 at the basolateral membrane of intestinal cells. In addition, we found that sgk-1(RNAi) induced unfolded protein response in the ER, suggesting at least an indirect role of SGK-1 early in the secretory pathway. We propose that SGK-1 function is required for lipid homeostasis and that it acts at different intracellular trafficking steps.
authors.affiliation: College of Life Sciences, Beijing Normal University, Beijing, China; National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China; Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Li
authors.affiliation: Growth and Development, Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Julia Kathrin
authors.initials: JK
authors.lastname: Stevens
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Chao-Xuan
authors.initials: CX
authors.lastname: Fan
authors.affiliation: Growth and Development, Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Spang
authors.affiliation: College of Life Sciences, Beijing Normal University, Beijing, China; National Institute of Biological Sciences, Beijing, Beijing, China; Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Meng-Qiu
authors.initials: MQ
authors.lastname: Dong
mesh_terms: D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D017346:Protein Serine-Threonine Kinases; C540745:Sgk-1 protein, C elegans