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Microtubule-Associated Protein EB3 Regulates IP3 Receptor Clustering and Ca(2+) Signaling in Endothelial Cells.

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Title: Microtubule-Associated Protein EB3 Regulates IP3 Receptor Clustering and Ca(2+) Signaling in Endothelial Cells.
Author(s): Geyer, M.; Huang, F.; Sun, Y.; Vogel, SM; Malik, AB; Taylor, CW; Komarova, YA
Abstract: The mechanisms by which the microtubule cytoskeleton regulates the permeability of endothelial barrier are not well understood. Here, we demonstrate that microtubule-associated end-binding protein 3 (EB3), a core component of the microtubule plus-end protein complex, binds to inositol 1,4,5-trisphosphate receptors (IP3Rs) through an S/TxIP EB-binding motif. In endothelial cells, α-thrombin, a pro-inflammatory mediator that stimulates phospholipase Cβ, increases the cytosolic Ca(2+) concentration and elicits clustering of IP3R3s. These responses, and the resulting Ca(2+)-dependent phosphorylation of myosin light chain, are prevented by depletion of either EB3 or mutation of the TxIP motif of IP3R3 responsible for mediating its binding to EB3. We also show that selective EB3 gene deletion in endothelial cells of mice abrogates α-thrombin-induced increase in endothelial permeability. We conclude that the EB3-mediated interaction of IP3Rs with microtubules controls the assembly of IP3Rs into effective Ca(2+) signaling clusters, which thereby regulate microtubule-dependent endothelial permeability.
Issue Date: 2015-07-07
Publisher: Elsevier
Citation Info: Geyer, M., Huang, F., Sun, Y., Vogel, S. M., Malik, A. B., Taylor, C. W. and Komarova, Y. A. Microtubule-Associated Protein EB3 Regulates IP3 Receptor Clustering and Ca2+ Signaling in Endothelial Cells. Cell Reports. 2015. 12(1): 79-89. DOI: 10.1016/j.celrep.2015.06.001.
Type: Article
Description: This is the copy of an article published in Cell Reports © 2015 Elsevier Publications.
ISSN: 2211-1247
Sponsor: Supported by NIH grants R01 HL103922 and Giles F. Filley Memorial Award to Y.A.K.; PO1 HL60678 to A.B.M.; T32 HL07829-17 and AHA AWARD 13PRE17090090 to M.G., and a Wellcome Trust Senior Investigator Award (101844) to C.W.T.
Date Available in INDIGO: 2016-02-17

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