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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 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.

SUBMITTER: Wang WA 

PROVIDER: S-EPMC5517566 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Wang Wen-An WA   Liu Wen-Xin WX   Durnaoglu Serpen S   Lee Sun-Kyung SK   Lian Jihong J   Lehner Richard R   Ahnn Joohong J   Agellon Luis B LB   Michalak Marek M  

Scientific reports 20170719 1


A direct link between Ca<sup>2+</sup> and lipid homeostasis has not been definitively demonstrated. In this study, we show that manipulation of ER Ca<sup>2+</sup> 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 Ca<sup>2+</sup> depleted cells remained fully functional and responsive to changes in cellular cholesterol status but differed unexpectedly in basal activity  ...[more]

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