Polycystin-1: a master regulator of intersecting cystic pathways.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially lethal monogenic disorder, with more than 12 million cases worldwide. The two causative genes for ADPKD, PKD1 and PKD2, encode protein products polycystin-1 (PC1) and polycystin-2 (PC2 or TRPP2), respectively. Recent data have shed light on the role of PC1 in regulating the severity of the cystic phenotypes in ADPKD, autosomal recessive polycystic kidney disease (ARPKD), and isolated autosomal dominant polycystic liver disease (ADPLD). These studies showed that the rate for cyst growth was a regulated trait, a process that can be either sped up or slowed down by alterations in functional PC1. These findings redefine the previous understanding that cyst formation occurs as an 'on-off' process. Here, we review these and other related studies with an emphasis on their translational implications for polycystic diseases.
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. Electronic address: sorin.fedeles@yale.edu.
Sorin V
SV
Fedeles
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
Anna-Rachel
AR
Gallagher
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA. Electronic address: stefan.somlo@yale.edu.
Stefan
S
Somlo
D000818:Animals; D003560:Cysts / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism*; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism*
D050396:TRPP Cation Channels
chaperone therapy; cyst progression; polycystic kidney disease; polycystic liver disease; polycystin-1 dosage; protein biogenesis