Recent advances in the cell biology of polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is a significant familial disorder, crossing multiple ethnicities as well as organ systems. The goal of understanding and, ultimately, curing ADPKD has fostered collaborative efforts among many laboratories, mustered on by the opportunity to probe fundamental cellular biology. Here we review what is known about ADPKD including well-accepted data such as the identification of the causative genes and the fact that PKD1 and PKD2 act in the same pathway, fairly well-accepted concepts such as the "two-hit hypothesis," and somewhat confusing information regarding polycystin-1 and -2 localization and protein interactions. Special attention is paid to the recently discovered role of the cilium in polycystic kidney disease and the model it suggests. Studying ADPKD is important, not only as an evaluation of a multisystem disorder that spans a lifetime, but as a testament to the achievements of modern biology and medicine.
Smyth
Brendan J
BJ
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Snyder
Richard W
RW
Balkovetz
Daniel F
DF
Lipschutz
Joshua H
JH
D000818:Animals; D002923:Cilia / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D050396:TRPP Cation Channels
D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels