The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth

نویسندگان

  • Bernhard Schermer
  • Cristina Ghenoiu
  • Malte Bartram
  • Roman Ulrich Müller
  • Fruzsina Kotsis
  • Martin Höhne
  • Wolfgang Kühn
  • Manuela Rapka
  • Roland Nitschke
  • Hanswalter Zentgraf
  • Manfred Fliegauf
  • Heymut Omran
  • Gerd Walz
  • Thomas Benzing
چکیده

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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عنوان ژورنال:
  • The Journal of Cell Biology

دوره 175  شماره 

صفحات  -

تاریخ انتشار 2006