title: The Rilp-like proteins Rilpl1 and Rilpl2 regulate ciliary membrane content.
abstract: The primary cilium is a microtubule-based structure found in most cell types in mammals. Disruption of cilium function causes a diverse set of human diseases collectively known as ciliopathies. We report that Rab effector-related proteins Rab-interacting lysosomal protein-like 1 (Rilpl1) and Rilpl2 regulate protein localization in the primary cilium. Rilpl2 was initially identified as up-regulated in ciliating mouse tracheal epithelial cells. Rilpl1 and Rilpl2 both localize to the primary cilium and centrosome, Rilpl1 specifically to the distal end of the mother centriole. Live-cell microscopy reveals that Rilpl2 primary cilium localization is dynamic and that it is associated with tubulovesicular structures at the base of the cilium. Depletion of Rilpl1 and Rilpl2 results in accumulation of signaling proteins in the ciliary membrane and prevents proper epithelial cell organization in three-dimensional culture. These data suggest that Rilp-like proteins function in regulation of ciliary membrane protein concentration by promoting protein removal from the primary cilium.
authors.affiliation: Department of Biology, Stanford University, Department of Genetics, Stanford School of Medicine, Stanford, CA 94305, USA.
authors.forename: Johanna R
authors.initials: JR
authors.lastname: Schaub
authors.forename: Tim
authors.initials: T
authors.lastname: Stearns
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018929:Cell Culture Techniques; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D002502:Centrioles / Q000378:metabolism / Q000648:ultrastructure; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006801:Humans; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D016415:Sequence Alignment; D015398:Signal Transduction; D014132:Trachea / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D020033:Protein Isoforms; C582397:Rilpl1 protein, mouse; C582398:Rilpl2 protein, mouse