Letter abstract
Nature Cell Biology 9, 588 - 595 (2007)
Published online: 22 April 2007 | doi:10.1038/ncb1579
pVHL and GSK3
are components of a primary cilium-maintenance signalling network
Claudio R. Thoma1,3,4, Ian J. Frew1,4, Christian R. Hoerner1, Matteo Montani2, Holger Moch2 & Wilhelm Krek1
Defects in the structure or function of the primary cilium, an antennae-like structure whose functional integrity has been linked to the suppression of uncontrolled kidney epithelial cell proliferation, are a common feature of genetic disorders characterized by kidney cysts1, 2. However, the mechanisms by which primary cilia are maintained remain poorly defined. von Hippel-Lindau (VHL) disease is characterized by the development of premalignant renal cysts and arises because of functional inactivation of the VHL tumour suppressor gene product, pVHL3, 4. Here, we show that pVHL and glycogen synthase kinase (GSK)3
are key components of an interlinked signalling pathway that maintains the primary cilium. Although inactivation of either pVHL or GSK3 alone did not affect cilia maintenance, their combined inactivation leads to loss of cilia. In VHL patients, GSK3 is subjected to inhibitory phosphorylation in renal cysts, but not in early VHL mutant lesions, and these cysts exhibit reduced frequencies of primary cilia. We propose that pVHL and GSK3 function together in a ciliary-maintenance signalling network, disruption of which enhances the vulnerability of cells to lose their cilia, thereby promoting cyst formation.
- Institute of Cell Biology, ETH Zurich, 8093 Zurich, Switzerland.
- Institute of Clinical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland.
- Life Science Zurich Graduate School, PhD Programme in Molecular Life Sciences, Universty of Zurich, 8057 Zurich, Switzerland.
- These authors contributed equally to this work.
Correspondence to: Wilhelm Krek1 e-mail: wilhelm.krek@cell.biol.ethz.ch
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