Cell Polarity and Cystic Diseases

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There was an interesting article and accompanying editorial in JASN this month about the role of polarity in the development of cystic renal diseases. The maintenance of epithelial cell polarity is vital for the normal functioning of the renal tubules and the usual interpretation of this is the way in which a cell is organized into basolateral and luminal compartments (e.g. in intercalated cells, there is a luminal H+ ATPase and a basolateral anion exchanger and it is this polarity that facilitates acid excretion). In a similar way, mislocalization of the Na-K-ATPase has been noted in patients with ADPKD and is a putative mechanism for cyst formation.

However, there is another facet to polarity which appears to be just as important – planar polarity – this is the correct orientation of cells and specialized structures within cells along the plane of the epithelial sheet. Much research is continuing into the genes responsible for the development and maintenance of polarity. One of the means by which a loss of planar polarity may induce the formation of cysts is through the loss or dysfunction of primary cilia.

The authors in JASN found that both a gain and loss of function mutation in ErbB4 led to a loss of cell polarity. Members of this receptor family have been shown to be responsible for the development of polarity in neurons and in certain cancers.

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