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The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth
Authors:Schermer Bernhard  Ghenoiu Cristina  Bartram Malte  Müller Roman Ulrich  Kotsis Fruzsina  Höhne Martin  Kühn Wolfgang  Rapka Manuela  Nitschke Roland  Zentgraf Hanswalter  Fliegauf Manfred  Omran Heymut  Walz Gerd  Benzing Thomas
Affiliation:Renal Division and 2Children's Hospital, University Hospital Freiburg, 79106 Freiburg, Germany.
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.
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