Study Challenges Current Thinking About Autosomal Dominant Polycystic Kidney Disease (ADPKD); New Research Shows That Lack of Polycystin-2 (PC2) Protein in Cells’ Endoplasmic Reticulum May Play Important Role

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic condition that can lead to kidney failure and that has no cure. Recent research published in the Journal of the Society of Nephrology (JASN) has revealed an over-looked mechanism that may contribute to this condition. The findings provide a better understanding of ADPKD and may lead to new treatment strategies. (Image shows normal-sized kidney at left and polycystic kidney on right). Mutations in the PKD1 gene, which codes for polycystin-1 (PC1), or in the PKD2 gene, which codes for polycystin-2 (PC2), cause most cases of ADPKD. The PC1 and PC2 proteins function as receptor-channel complexes for calcium and other ions, and they are found in cell structures called primary cilia. Primary cilia are tiny, fingerlike projections from cells that line the small tubes where urine is formed. Loss of PC1 or PC2 in cilia is believed to be central to the pathogenesis of cyst formation that’s a hallmark of ADPKD. PC1 and PC2 can be expressed in other locations, however, and it’s unclear if the normal forms of these proteins are also important for preventing ADPKD. To investigate, Chou-Long Huang, MD, PhD (University of Iowa Carver College of Medicine) and his colleagues examined the role of PC2 in the endoplasmic reticulum (ER), a structure within cells that’s involved in protein and lipid synthesis. The team found that normal PC2 in the ER is important for maintaining kidney health and that its loss can lead to cyst formation.

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