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.
The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth
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.
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; The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth . J Cell Biol 20 November 2006; 175 (4): 547–554. doi: https://doi.org/10.1083/jcb.200605092
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