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钙网织蛋白缺失揭示了钙在调节细胞脂质稳态中的关键作用。

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

机构信息

Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.

Department of Life Sciences, Research Institute for Natural Sciences, BK21 Plus Life Science for BDR Team, Research Institute of Natural Science, Hanyang University, Seoul, 133-791, South Korea.

出版信息

Sci Rep. 2017 Jul 19;7(1):5941. doi: 10.1038/s41598-017-05734-x.

DOI:10.1038/s41598-017-05734-x
PMID:28725049
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5517566/
Abstract

A direct link between Ca and lipid homeostasis has not been definitively demonstrated. In this study, we show that manipulation of ER Ca 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 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 Ca in determining the reference set-point for controlling cellular lipid homeostasis. We propose that ER Ca status is an important determinant of the basal sensitivity of the sterol sensing mechanism inherent to the SREBP processing pathway.

摘要

钙(Ca)和脂质动态平衡之间没有明确的直接联系。在这项研究中,我们表明内质网 Ca 的操纵会导致细胞内未酯化胆固醇的一部分重新分布到不可用于 SREBP 复合物的池子里。内质网 Ca 耗竭细胞中的 SREBP 加工途径仍然保持完全功能,并且对细胞胆固醇状态的变化有反应,但出乎意料的是在基础活性方面有所不同。这些发现确立了 Ca 在确定控制细胞脂质动态平衡的参考设定点方面的作用。我们提出内质网 Ca 状态是固醇感应机制固有 SREBP 加工途径的基础敏感性的重要决定因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/699b432d39de/41598_2017_5734_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/7499636f49fa/41598_2017_5734_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/21c223e1edbe/41598_2017_5734_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/79fdab88f4dc/41598_2017_5734_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/36cb93c9d397/41598_2017_5734_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/327af6c70814/41598_2017_5734_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/ae15b2c6d13f/41598_2017_5734_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/c0c571cc8fe4/41598_2017_5734_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/699b432d39de/41598_2017_5734_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/7499636f49fa/41598_2017_5734_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/21c223e1edbe/41598_2017_5734_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/79fdab88f4dc/41598_2017_5734_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/36cb93c9d397/41598_2017_5734_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/327af6c70814/41598_2017_5734_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/ae15b2c6d13f/41598_2017_5734_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/c0c571cc8fe4/41598_2017_5734_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7966/5517566/699b432d39de/41598_2017_5734_Fig8_HTML.jpg

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