@article{02bf388f5f414cb280b3ff269e38641a,
title = "Polycystin 2 is increased in disease to protect against stress-induced cell death",
abstract = "Polycystin 2 (PC2 or TRPP1, formerly TRPP2) is a calcium-permeant Transient Receptor Potential (TRP) cation channel expressed primarily on the endoplasmic reticulum (ER) membrane and primary cilia of all cell and tissue types. Despite its ubiquitous expression throughout the body, studies of PC2 have focused primarily on its role in the kidney, as mutations in PC2 lead to the development of autosomal dominant polycystic kidney disease (ADPKD), a debilitating condition for which there is no cure. However, the endogenous role that PC2 plays in the regulation of general cellular homeostasis remains unclear. In this study, we measure how PC2 expression changes in different pathological states, determine that its abundance is increased under conditions of cellular stress in multiple tissues including human disease, and conclude that PC2-deficient cells have increased susceptibility to cell death induced by stress. Our results offer new insight into the normal function of PC2 as a ubiquitous stress-sensitive protein whose expression is up-regulated in response to cell stress to protect against pathological cell death in multiple diseases.",
author = "Brill, {Allison L.} and Fischer, {Tom T.} and Walters, {Jennifer M.} and Arnaud Marlier and Sewanan, {Lorenzo R.} and Wilson, {Parker C.} and Johnson, {Eric K.} and Gilbert Moeckel and Cantley, {Lloyd G.} and Campbell, {Stuart G.} and Nerbonne, {Jeanne M.} and Chung, {Hee Jung} and Robert, {Marie E.} and Ehrlich, {Barbara E.}",
note = "Funding Information: We thank Qi Wang and Dr. Xiaoyong Yang for kindly providing liver cDNA samples from ND-and HFD-fed mice. We thank Dr. Bentley Lim, Eunice Cho (Yale University), and Dr. Olga Buzovetsky (The Rockefeller University) for helpful discussions and edits. We thank Esther Giehl (Charit{\'e} – Universit{\"a}tsmedizin Berlin) for the contribution of saline-and ISO-treated murine hearts. Federal and NIH grant support is acknowledged: 5P01DK057751 and P30DK090744 (B.E.E.), F31DK118836 (A.L.B.), 1R01NS083402 and 1R01NS097610 (H.J.C.), T32GM007205 (L.R.S.), and GM007324. We acknowledge the use of the Yale Center for Cellular and Molecular Imaging (NIH grants 5P30DK034989 and OD020142). L.R.S. was supported by a P.D. Soros Fellowship for New Americans. WT and PC2 KO mIMCD-3 cells were created by members of the George M. O{\textquoteright}Brien Kidney Center at Yale (P30 DK079310). T.T.F. was supported by a scholarship from the German Academic Scholarship Foundation. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41598-019-57286-x",
language = "English (US)",
volume = "10",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}