NDLI: Regulation of Store-Operated Calcium Entry by FK506-Binding Immunophilins

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Regulation of Store-Operated Calcium Entry by FK506-Binding Immunophilins

Content Provider	PubMed Central
Author	Kadeba, Pierre I. Vasauskas, Audrey A. Chen, Hairu Wu, Songwei Scammell, Jonathan G. Cioffi, Donna L.
Copyright Year	2012
Abstract	Calcium entry from the extracellular space into cells is an important signaling mechanism in both physiological and pathophysiological functions. In non-excitable cells, store-operated calcium (SOC) entry represents a principal mode of calcium entry. Activation of SOC entry in pulmonary artery endothelial cells leads to the formation of inter-endothelial cell gaps and subsequent endothelial barrier disruption. Regulation of endothelial SOC entry is poorly understood. In this work, we identify two large molecular weight immunophilins, FKBP51 and FKBP52, as novel regulators of SOC entry in endothelial cells. Using cell fractionation studies and immunocytochemistry we determined that a fraction of these largely cytosolic proteins localize to the plasma membrane where SOC entry channels are found. That FKBP51 and FKBP52 associate with SOC entry channel protein complexes was supported by co-precipitation of the immunophilins with TRPC4, a subunit of the calcium-selective, SOC entry channel I SOC. Dexamethasone-induced upregulation of FKBP51 expression in pulmonary artery endothelial cells reduced global SOC entry as well as I SOC. Similar results were observed when FKBP51 was over-expressed in an inducible HEK293 cell line. On the other hand, when FKBP52 was over-expressed SOC entry was enhanced. When expression of FKBP52 was inhibited, SOC entry was decreased. Collectively, our observations support regulatory roles for these large molecular weight immunophilins in which FKBP51 inhibits, whereas FKBP52 enhances, SOC entry in endothelial cells.
Related Links	http://dx.doi.org/10.1016/j.ceca.2012.12.008
Ending Page	285
Page Count	11
Starting Page	275
File Format	PDF
ISSN	01434160
e-ISSN	15321991
Journal	Cell calcium
Issue Number	4
Volume Number	53
Language	English
Publisher Date	2013-04-01
Access Restriction	Open
Subject Keyword	Cell Biology Physiology Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Physiology Molecular Biology

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