Allele-specific regulation of primary cilia function by the von Hippel-Lindau tumor suppressor - PubMed (original) (raw)
Allele-specific regulation of primary cilia function by the von Hippel-Lindau tumor suppressor
Martijn P Lolkema et al. Eur J Hum Genet. 2008 Jan.
Abstract
Patients with von Hippel-Lindau (VHL) disease often develop VHL-/- kidney cysts, which possibly progress into clear-cell renal carcinomas (ccRCCs). Recent data link the VHL gene product to formation of the primary cilium, an organelle that extends apically into the renal lumen. Exactly how VHL induces ciliogenesis or function is unknown. Here, we demonstrate that ciliary assembly and mechanotransduction is rapidly restored in VHL-/- ccRCC cells upon ectopic reconstitution of wild-type - but not variant alleles of - VHL. These data support and expand recent studies implicating a role for VHL in the initiation of ciliogenesis. Furthermore, reduction of cellular levels of VHL in this cell system was associated with fewer ciliated cells, suggesting a role for VHL in ciliary maintenance.
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