Platelet-derived growth factor maintains stored calcium through a nonclustering Orai1 mechanism but evokes clustering if the endoplasmic reticulum is stressed by store depletion.

Circulation Research
Lynn McKeownDavid J Beech

Abstract

Calcium entry through Orai1 channels drives vascular smooth muscle cell migration and neointimal hyperplasia. The channels are activated by the important growth factor platelet-derived growth factor (PDGF). Channel activation is suggested to depend on store depletion, which redistributes and clusters stromal interaction molecule 1 (STIM1), which then coclusters and activates Orai1. To determine the relevance of STIM1 and Orai1 redistribution in PDGF responses. Vascular smooth muscle cells were cultured from human saphenous vein. STIM1 and Orai1 were tagged with green and red fluorescent proteins to track them in live cells. Under basal conditions, the proteins were mobile but mostly independent of each other. Inhibition of sarco-endoplasmic reticulum calcium ATPase led to store depletion and dramatic redistribution of STIM1 and Orai1 into coclusters. PDGF did not evoke redistribution, even though it caused calcium release and Orai1-mediated calcium entry in the same time period. After chemical blockade of Orai1-mediated calcium entry, however, PDGF caused redistribution. Similarly, mutagenic disruption of calcium flux through Orai1 caused PDGF to evoke redistribution, showing that calcium flux through the wild-type channels had...Continue Reading

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Citations

Mar 21, 2013·Science Signaling·Thomas Gudermann, Dirk Steinritz
Jul 24, 2013·Molecular and Cellular Biology·Xuexin ZhangMohamed Trebak
Jul 29, 2015·Cell Calcium·Patrick G Hogan
Dec 15, 2012·Biochemical and Biophysical Research Communications·Dan StrattonJameel M Inal
Jun 23, 2012·Circulation Research·Kimberly A Smith, Jason X-J Yuan
Jul 15, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Jing LiDavid J Beech
May 18, 2017·Frontiers in Oncology·Insa M A Wolf, Andreas H Guse
May 4, 2021·Frontiers in Cell and Developmental Biology·Heba ShawerMarc A Bailey

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