The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Carrier Proteins, Cell Polarity, Cilia, Dogs, Epithelial Cells, Humans, Kidney, Lentivirus, Membrane Proteins, Mice, Microtubules, Morphogenesis, Phenotype, Protein Binding, Protein Kinase C, Protein Transport, Von Hippel-Lindau Tumor Suppressor Protein
Adaptor Proteins, Signal Transducing, Animals, Carrier Proteins, Cell Polarity, Cilia, Dogs, Epithelial Cells, Humans, Kidney, Lentivirus, Membrane Proteins, Mice, Microtubules, Morphogenesis, Phenotype, Protein Binding, Protein Kinase C, Protein Transport, Von Hippel-Lindau Tumor Suppressor Protein
J. Cell Biol.
Date: Nov. 20, 2006
PubMed ID: 17101696
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