Polycystic kidney disease: novel insights into polycystin function

Lingfei Luo; Sudipto Roy; Li Li; Ming Ma

doi:10.1016/j.molmed.2023.01.005

Polycystic kidney disease: novel insights into polycystin function

Trends Mol Med. 2023 Apr;29(4):268-281. doi: 10.1016/j.molmed.2023.01.005. Epub 2023 Feb 15.

Authors

Lingfei Luo¹, Sudipto Roy², Li Li³, Ming Ma⁴

Affiliations

¹ Institute of Developmental Biology and Regenerative Medicine, Southwest University, Beibei, Chongqing, 400715, China.
² Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Proteos, 61 Biopolis Drive, Singapore, 138673, Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore, 119288, Singapore; Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore, 117543, Singapore.
³ Institute of Developmental Biology and Regenerative Medicine, Southwest University, Beibei, Chongqing, 400715, China; Research Center of Stem cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China.
⁴ Institute of Developmental Biology and Regenerative Medicine, Southwest University, Beibei, Chongqing, 400715, China. Electronic address: skymaming@swu.edu.cn.

PMID: 36805211
DOI: 10.1016/j.molmed.2023.01.005

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening monogenic disease caused by mutations in PKD1 and PKD2 that encode polycystin 1 (PC1) and polycystin 2 (PC2). PC1/2 localize to cilia of renal epithelial cells, and their function is believed to embody an inhibitory activity that suppresses the cilia-dependent cyst activation (CDCA) signal. Consequently, PC deficiency results in activation of CDCA and stimulates cyst growth. Recently, re-expression of PCs in established cysts has been shown to reverse PKD. Thus, the mode of action of PCs resembles a 'counterbalance in cruise control' to maintain lumen diameter within a designated range. Herein we review recent studies that point to novel arenas for future PC research with therapeutic potential for ADPKD.

Keywords: ADPKD; CDCA; cation channel; cilia; lumen diameter control; polycystin.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Cysts* / complications
Humans
Kidney / metabolism
Polycystic Kidney Diseases* / complications
Polycystic Kidney Diseases* / genetics
Polycystic Kidney, Autosomal Dominant* / genetics
Signal Transduction
TRPP Cation Channels / genetics
TRPP Cation Channels / metabolism

Substances

TRPP Cation Channels