title: The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth.
abstract: Cilia are specialized organelles that play an important role in several biological processes, including mechanosensation, photoperception, and osmosignaling. Mutations in proteins localized to cilia have been implicated in a growing number of human diseases. In this study, we demonstrate that the von Hippel-Lindau (VHL) protein (pVHL) is a ciliary protein that controls ciliogenesis in kidney cells. Knockdown of pVHL impeded the formation of cilia in mouse inner medullary collecting duct 3 kidney cells, whereas the expression of pVHL in VHL-negative renal cancer cells rescued the ciliogenesis defect. Using green fluorescent protein-tagged end-binding protein 1 to label microtubule plus ends, we found that pVHL does not affect the microtubule growth rate but is needed to orient the growth of microtubules toward the cell periphery, a prerequisite for the formation of cilia. Furthermore, pVHL interacts with the Par3-Par6-atypical PKC complex, suggesting a mechanism for linking polarity pathways to microtubule capture and ciliogenesis.
authors.affiliation: Renal Division and 2Children's Hospital, University Hospital Freiburg, 79106 Freiburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schermer
authors.forename: Cristina
authors.initials: C
authors.lastname: Ghenoiu
authors.forename: Malte
authors.initials: M
authors.lastname: Bartram
authors.forename: Roman Ulrich
authors.initials: RU
authors.lastname: Müller
authors.forename: Fruzsina
authors.initials: F
authors.lastname: Kotsis
authors.forename: Martin
authors.initials: M
authors.lastname: Höhne
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kühn
authors.forename: Manuela
authors.initials: M
authors.lastname: Rapka
authors.forename: Roland
authors.initials: R
authors.lastname: Nitschke
authors.forename: Hanswalter
authors.initials: H
authors.lastname: Zentgraf
authors.forename: Manfred
authors.initials: M
authors.lastname: Fliegauf
authors.forename: Heymut
authors.initials: H
authors.lastname: Omran
authors.forename: Gerd
authors.initials: G
authors.lastname: Walz
authors.forename: Thomas
authors.initials: T
authors.lastname: Benzing
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D016764:Cell Polarity; D002923:Cilia / Q000502:physiology* / Q000648:ultrastructure; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000166:cytology; D016086:Lentivirus; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009024:Morphogenesis; D010641:Phenotype; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D008565:Membrane Proteins; C471157:PARD3B protein, human; C499657:PARD6A protein, human; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D011493:Protein Kinase C