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Published online 13 November 2006. doi:10.1083/jcb.200605092
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 175, Number 4, 547-554
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 The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth

Bernhard Schermer1, Cristina Ghenoiu1, Malte Bartram1, Roman Ulrich Müller1, Fruzsina Kotsis1, Martin Höhne1, Wolfgang Kühn1, Manuela Rapka1, Roland Nitschke3, Hanswalter Zentgraf4, Manfred Fliegauf2, Heymut Omran2, Gerd Walz1, and Thomas Benzing1

1 Renal Division and 2 Children's Hospital, University Hospital Freiburg, 79106 Freiburg, Germany
3 Life Imaging Center, Institute of Biology, University of Freiburg, 79104 Freiburg, Germany
4 Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany

Correspondence to Thomas Benzing: thomas.benzing{at}uniklinik-freiburg.de

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.

B. Schermer, C. Ghenoiu, and M. Bartram contributed equally to this paper.

Abbreviations used in this paper: aPKC, atypical PKC; EB1, end-binding protein 1; HEK, human embryonic kidney; IFT, intraflagellar transport; mIMCD, mouse inner medullary collecting duct; pVHL, VHL protein; RCC, renal cell carcinoma; shRNA, short hairpin RNA; UTR, untranslated region; VHL, von Hippel-Lindau.


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