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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

OFD1 is a centrosomal/basal body protein expressed during mesenchymal-epithelial transition in human nephrogenesis.

OFD1 is the gene responsible for the oral-facial-digital syndrome type 1, a cause of inherited cystic renal disease. The protein contains an N-terminal LisH motif, considered important in microtubule dynamics, and several putative coiled-coil domains. This study used a combination of microscopic, biochemical, and overexpression approaches to demonstrate that OFD1 protein is a core component of the human centrosome throughout the cell cycle. Using a series of GFP-OFD1 deletion constructs, it was determined that the N-terminus containing the LisH domain is not required for centrosomal localization; however, coiled-coil domains are critical, with at least two being necessary for centrosomal targeting. Importantly, most reported OFD1 mutations are predicted to cause protein truncation with loss of coiled-coil domains, presumably leading to loss of centrosomal localization. Kidney development constitutes a classic model of mesenchymal-epithelial transformation. By immunoprobing human metanephroi and kidney epithelial lines, it was found that, during acquisition of epithelial polarity, OFD1 became localized to the apical zone of nephron precursor cells and then to basal bodies at the origin of primary cilia in fully differentiated epithelia. These striking patterns of OFD1 localization within cells place the protein at key sites, where it may play roles not only in microtubule organization (centrosomal function) but also in mechanosensation of urine flow (a primary ciliary function).[1]

References

  1. OFD1 is a centrosomal/basal body protein expressed during mesenchymal-epithelial transition in human nephrogenesis. Romio, L., Fry, A.M., Winyard, P.J., Malcolm, S., Woolf, A.S., Feather, S.A. J. Am. Soc. Nephrol. (2004) [Pubmed]
 
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