Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis

Abstract A direct link between Ca2+ and lipid homeostasis has not been definitively demonstrated. In this study, we show that manipulation of ER Ca2+ causes the re-distribution of a portion of the intracellular unesterified cholesterol to a pool that is not available to the SCAP-SREBP complex. The S...

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Autores principales:	Wen-An Wang, Wen-Xin Liu, Serpen Durnaoglu, Sun-Kyung Lee, Jihong Lian, Richard Lehner, Joohong Ahnn, Luis B. Agellon, Marek Michalak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/181ac3ffb8594bf0b12bfef6d8cefed5
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spelling	oai:doaj.org-article:181ac3ffb8594bf0b12bfef6d8cefed52021-12-02T15:06:22ZLoss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis10.1038/s41598-017-05734-x2045-2322https://doaj.org/article/181ac3ffb8594bf0b12bfef6d8cefed52017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05734-xhttps://doaj.org/toc/2045-2322Abstract A direct link between Ca2+ and lipid homeostasis has not been definitively demonstrated. In this study, we show that manipulation of ER Ca2+ causes the re-distribution of a portion of the intracellular unesterified cholesterol to a pool that is not available to the SCAP-SREBP complex. The SREBP processing pathway in ER Ca2+ depleted cells remained fully functional and responsive to changes in cellular cholesterol status but differed unexpectedly in basal activity. These findings establish the role of Ca2+ in determining the reference set-point for controlling cellular lipid homeostasis. We propose that ER Ca2+ status is an important determinant of the basal sensitivity of the sterol sensing mechanism inherent to the SREBP processing pathway.Wen-An WangWen-Xin LiuSerpen DurnaogluSun-Kyung LeeJihong LianRichard LehnerJoohong AhnnLuis B. AgellonMarek MichalakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wen-An Wang Wen-Xin Liu Serpen Durnaoglu Sun-Kyung Lee Jihong Lian Richard Lehner Joohong Ahnn Luis B. Agellon Marek Michalak Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis
description	Abstract A direct link between Ca2+ and lipid homeostasis has not been definitively demonstrated. In this study, we show that manipulation of ER Ca2+ causes the re-distribution of a portion of the intracellular unesterified cholesterol to a pool that is not available to the SCAP-SREBP complex. The SREBP processing pathway in ER Ca2+ depleted cells remained fully functional and responsive to changes in cellular cholesterol status but differed unexpectedly in basal activity. These findings establish the role of Ca2+ in determining the reference set-point for controlling cellular lipid homeostasis. We propose that ER Ca2+ status is an important determinant of the basal sensitivity of the sterol sensing mechanism inherent to the SREBP processing pathway.
format	article
author	Wen-An Wang Wen-Xin Liu Serpen Durnaoglu Sun-Kyung Lee Jihong Lian Richard Lehner Joohong Ahnn Luis B. Agellon Marek Michalak
author_facet	Wen-An Wang Wen-Xin Liu Serpen Durnaoglu Sun-Kyung Lee Jihong Lian Richard Lehner Joohong Ahnn Luis B. Agellon Marek Michalak
author_sort	Wen-An Wang
title	Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis
title_short	Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis
title_full	Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis
title_fullStr	Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis
title_full_unstemmed	Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis
title_sort	loss of calreticulin uncovers a critical role for calcium in regulating cellular lipid homeostasis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/181ac3ffb8594bf0b12bfef6d8cefed5
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Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis

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