Calcium Signaling in Polycystic Kidney Disease- Cell Death and Survival

Overview

Journal Cell Calcium

Publisher Elsevier

Specialties Cell Biology
Endocrinology

Date 2023 Apr 6

PMID 37023534

Authors

Karla M Marquez-Nogueras

Virdjinija Vuchkovska

Ivana Y Kuo

Affiliations

Soon will be listed here.

Abstract

Polycystic kidney disease is typified by cysts in the kidney and extra-renal manifestations including hypertension and heart failure. The main genetic underpinning this disease are loss-of function mutations to the two polycystin proteins, polycystin 1 and polycystin 2. Molecularly, the disease is characterized by changes in multiple signaling pathways including down regulation of calcium signaling, which, in part, is contributed by the calcium permeant properties of polycystin 2. These signaling pathways enable the cystic cells to survive and avoid cell death. This review focuses on the studies that have emerged in the past 5 years describing how the structural insights gained from PC-1 and PC-2 inform the calcium dependent molecular pathways of autophagy and the unfolded protein response that are regulated by the polycystin proteins and how it leads to cell survival and/or cell death.

Citing Articles

The mutual interaction of TRPC5 channel with polycystin proteins.

Kwak M, Kang H, Kim J, Hong Y, Jeong B, Myeong J Korean J Physiol Pharmacol. 2024; 29(1):93-108.

PMID: 39523478 PMC: 11694000. DOI: 10.4196/kjpp.24.265.

Lichner Z, Ding M, Khare T, Dan Q, Benitez R, Praszner M Cells. 2024; 13(11.

PMID: 38891116 PMC: 11172104. DOI: 10.3390/cells13110984.

Calcium signalling and transport in the kidney.

Staruschenko A, Alexander R, Caplan M, Ilatovskaya D Nat Rev Nephrol. 2024; 20(8):541-555.

PMID: 38641658 DOI: 10.1038/s41581-024-00835-z.

Autosomal Dominant Polycystic Kidney Disease: Extrarenal Involvement.

Righini M, Mancini R, Busutti M, Buscaroli A Int J Mol Sci. 2024; 25(5).

PMID: 38473800 PMC: 10932244. DOI: 10.3390/ijms25052554.

References

Perico N, Antiga L, Caroli A, Ruggenenti P, Fasolini G, Cafaro M . Sirolimus therapy to halt the progression of ADPKD. J Am Soc Nephrol. 2010; 21(6):1031-40. PMC: 2900967. DOI: 10.1681/ASN.2009121302. View

Chebib F, Perrone R, Chapman A, Dahl N, Harris P, Mrug M . A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan. J Am Soc Nephrol. 2018; 29(10):2458-2470. PMC: 6171265. DOI: 10.1681/ASN.2018060590. View

Schreiber R, Buchholz B, Kraus A, Schley G, Scholz J, Ousingsawat J . Lipid Peroxidation Drives Renal Cyst Growth through Activation of TMEM16A. J Am Soc Nephrol. 2019; 30(2):228-242. PMC: 6362630. DOI: 10.1681/ASN.2018010039. View

Su Q, Hu F, Ge X, Lei J, Yu S, Wang T . Structure of the human PKD1-PKD2 complex. Science. 2018; 361(6406). DOI: 10.1126/science.aat9819. View

Boletta A . Emerging evidence of a link between the polycystins and the mTOR pathways. Pathogenetics. 2009; 2(1):6. PMC: 2781793. DOI: 10.1186/1755-8417-2-6. View

Levine B, Kroemer G . Biological Functions of Autophagy Genes: A Disease Perspective. Cell. 2019; 176(1-2):11-42. PMC: 6347410. DOI: 10.1016/j.cell.2018.09.048. View

Yuan S, Zhao L, Brueckner M, Sun Z . Intraciliary calcium oscillations initiate vertebrate left-right asymmetry. Curr Biol. 2015; 25(5):556-67. PMC: 4469357. DOI: 10.1016/j.cub.2014.12.051. View

Brill A, Fischer T, Walters J, Marlier A, Sewanan L, Wilson P . Polycystin 2 is increased in disease to protect against stress-induced cell death. Sci Rep. 2020; 10(1):386. PMC: 6962458. DOI: 10.1038/s41598-019-57286-x. View

Fedeles S, So J, Shrikhande A, Lee S, Gallagher A, Barkauskas C . Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity. J Clin Invest. 2015; 125(5):1955-67. PMC: 4463201. DOI: 10.1172/JCI78863. View

10.

Waters A, Beales P . Ciliopathies: an expanding disease spectrum. Pediatr Nephrol. 2011; 26(7):1039-56. PMC: 3098370. DOI: 10.1007/s00467-010-1731-7. View

11.

Winokurow N, Schumacher S . A role for polycystin-1 and polycystin-2 in neural progenitor cell differentiation. Cell Mol Life Sci. 2019; 76(14):2851-2869. PMC: 11105687. DOI: 10.1007/s00018-019-03072-x. View

12.

Wheway G, Nazlamova L, Hancock J . Signaling through the Primary Cilium. Front Cell Dev Biol. 2018; 6:8. PMC: 5809511. DOI: 10.3389/fcell.2018.00008. View

13.

Marquez-Nogueras K, Vuchkovska V, DiNello E, Osorio-Valencia S, Kuo I . Polycystin-2 (PC2) is a key determinant of in vitro myogenesis. Am J Physiol Cell Physiol. 2022; 323(2):C333-C346. PMC: 9291421. DOI: 10.1152/ajpcell.00159.2021. View

14.

Fick G, Johnson A, HAMMOND W, Gabow P . Causes of death in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 1995; 5(12):2048-56. DOI: 10.1681/ASN.V5122048. View

15.

. The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16. The European Polycystic Kidney Disease Consortium. Cell. 1994; 77(6):881-94. DOI: 10.1016/0092-8674(94)90137-6. View

16.

Kuo I, Chapman A . Polycystins, ADPKD, and Cardiovascular Disease. Kidney Int Rep. 2020; 5(4):396-406. PMC: 7136326. DOI: 10.1016/j.ekir.2019.12.007. View

17.

Nauli S, Alenghat F, Luo Y, Williams E, Vassilev P, Li X . Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet. 2003; 33(2):129-37. DOI: 10.1038/ng1076. View

18.

Zhou X, Xiong H, Lu Y, Geng M, Lu Y, Zhang L . PKD2 deficiency suppresses amino acid biosynthesis in ADPKD by impairing the PERK-TBL2-eIF2ɑ-ATF4 pathway. Biochem Biophys Res Commun. 2021; 561:73-79. DOI: 10.1016/j.bbrc.2021.05.012. View

19.

CALVET J . Polycystic kidney disease: primary extracellular matrix abnormality or defective cellular differentiation?. Kidney Int. 1993; 43(1):101-8. DOI: 10.1038/ki.1993.17. View

20.

Joly D, Ishibe S, Nickel C, Yu Z, Somlo S, Cantley L . The polycystin 1-C-terminal fragment stimulates ERK-dependent spreading of renal epithelial cells. J Biol Chem. 2006; 281(36):26329-39. DOI: 10.1074/jbc.M601373200. View