title: Interaction between FIP5 and SNX18 regulates epithelial lumen formation.
abstract: During the morphogenesis of the epithelial lumen, apical proteins are thought to be transported via endocytic compartments to the site of the forming lumen, although the machinery mediating this transport remains to be elucidated. Rab11 GTPase and its binding protein, FIP5, are important regulators of polarized endocytic transport. In this study, we identify sorting nexin 18 as a novel FIP5-interacting protein and characterize the role of FIP5 and SNX18 in epithelial lumen morphogenesis. We show that FIP5 mediates the transport of apical proteins from apical endosomes to the apical plasma membrane and, along with SNX18, is required for the early stages of apical lumen formation. Furthermore, both proteins bind lipids, and FIP5 promotes the capacity of SNX18 to tubulate membranes, which implies a role for FIP5 and SNX18 in endocytic carrier formation and/or scission. In summary, the present findings support the hypothesis that this FIP5-SNX18 complex plays a pivotal role in the polarized transport of apical proteins during apical lumen initiation in epithelial cells.
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Carly
authors.initials: C
authors.lastname: Willenborg
authors.forename: Jian
authors.initials: J
authors.lastname: Jing
authors.forename: Christine
authors.initials: C
authors.lastname: Wu
authors.forename: Hugo
authors.initials: H
authors.lastname: Matern
authors.forename: Jerome
authors.initials: J
authors.lastname: Schaack
authors.forename: Jemima
authors.initials: J
authors.lastname: Burden
authors.forename: Rytis
authors.initials: R
authors.lastname: Prekeris
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001693:Biological Transport, Active / Q000502:physiology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009024:Morphogenesis / Q000502:physiology; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D046912:Multiprotein Complexes; C485422:RAB11FIP5 protein, human; C530791:SNX18 protein, human; D058305:Sorting Nexins