@article{f984aeae2cfa4c80a203d5f858f0a554,
title = "Calcium flux control by Pacs1-Wdr37 promotes lymphocyte quiescence and lymphoproliferative diseases",
abstract = "Endoplasmic reticulum (ER) calcium (Ca2+) stores are critical to proteostasis, intracellular signaling, and cellular bioenergetics. Through forward genetic screening in mice, we identified two members of a new complex, Pacs1 and Wdr37, which are required for normal ER Ca2+ handling in lymphocytes. Deletion of Pacs1 or Wdr37 caused peripheral lymphopenia that was linked to blunted Ca2+ release from the ER after antigen receptor stimulation. Pacs1-deficient cells showed diminished inositol triphosphate receptor expression together with increased ER and oxidative stress. Mature Pacs1−/− B cells proliferated and died in vivo under lymphocyte replete conditions, indicating spontaneous loss of cellular quiescence. Disruption of Pacs1-Wdr37 did not diminish adaptive immune responses, but potently suppressed lymphoproliferative disease models by forcing loss of quiescence. Thus, Pacs1-Wdr37 plays a critical role in stabilizing lymphocyte populations through ER Ca2+ handling and presents a new target for lymphoproliferative disease therapy.",
keywords = "Pacs1, Wdr37, calcium homeostasis, lymphocyte quiescence, lymphoproliferative disease",
author = "Evan Nair-Gill and Massimo Bonora and Xue Zhong and Aijie Liu and Amber Miranda and Nathan Stewart and Sara Ludwig and Jamie Russell and Thomas Gallagher and Paolo Pinton and Bruce Beutler",
note = "Funding Information: We thank Luming Chen for assistance with making the figures and insightful comments. We thank the following for their valuable assistance: Stephanie Arnett and Sheila Davis for mouse breeding, Diantha La Vine for the summary illustration, the UT Southwestern Proteomics Core for mass spectrometry, and Marcel Mettlen for live cell imaging. Funding for this project was provided by the Rheumatology Research Foundation Tob{\'e} and Stephen E. Malawista, MD Endowment in Academic Rheumatology (E.N.‐G.), NIH grants R01 AI125581 (B.B.) and U19 AI100627 (B.B.), and the Lyda Hill Foundation (B.B.). Funding Information: We thank Luming Chen for assistance with making the figures and insightful comments. We thank the following for their valuable assistance: Stephanie Arnett and Sheila Davis for mouse breeding, Diantha La Vine for the summary illustration, the UT Southwestern Proteomics Core for mass spectrometry, and Marcel Mettlen for live cell imaging. Funding for this project was provided by the Rheumatology Research Foundation Tob? and Stephen E. Malawista, MD Endowment in Academic Rheumatology (E.N.-G.), NIH grants R01 AI125581 (B.B.) and U19 AI100627 (B.B.), and the Lyda Hill Foundation (B.B.). Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = may,
day = "3",
doi = "10.15252/embj.2020104888",
language = "English (US)",
volume = "40",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "9",
}