Progress in the understanding of polycystic kidney disease.

The function of polycystin proteins and the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) are not well understood. Studies published in 2018 made important contributions to the understanding of genetic mechanisms, the structure of the polycystin complex and the roles of G-protein signalling and the immune system in ADPKD. The identification of high levels of somatic mutations in PKD1 and PKD2 in autosomal dominant polycystic kidney disease (ADPKD) cysts demonstrates an important role of polycystin loss in cyst progression1.A high-resolution cryogenic electron microscopy structure of the polycystin 1-polycystin 2 (PC1-PC2) complex provides insights into polycystin function and suggests that this complex does not form a functional Ca2+ permeable channel2.PC1 acts as a G-protein coupled receptor (GPCR) that binds α subunits; loss of the G-protein binding domain of PC1 causes GPCR hyper-reactivity, suggesting possible treatment options for ADPKD3.Cilia actively promote chemokine signalling and inflammation via a pathway that promotes monocyte chemoattractant protein 1 (MCP1) expression; this pathway can be suppressed by a module involving LKB1, PC1 and nephronophthisis-associated proteins4.Expression of MCP1 promotes macrophage accumulation and cystic dilatation; blocking the MCP1 receptor might be an advantageous strategy for the treatment of ADPKD5. [ABSTRACT FROM AUTHOR]