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- Title
Microtubule motors regulate activation of the Ca<sup>2+</sup>-selective store-operated current, l<sub>so</sub>, important for controlling lung endothelial cell barrier function.
- Authors
Songwei Wu; Hairu Chen; King, Judy; Alexeyev, Mikhail; Moore, Timothy; Stevens, Troy; Balczon, Ronald
- Abstract
While Ca2+ store depletion activates a Ca2+-selective store-operated current, ISOC, in pulmonary artery endothelial cells (PAECs) that is important for dislodging cell-cell apposition and increasing permeability, Ca2+ store depletion neither directly activates ISOC nor increases permeability in pulmonary microvascular endothelial cells (PMVECs). Since ISOC activation requires a close coupling between. endoplasmic reticulum (ER) and plasma membrane, and ER exhibits an anterograde distribution in PAECs when compared to PMVECs, we hypothesized that ER to plasma membrane coupling is an important determinant of ISOC activation in PAECs and PMVECs. Previously, we demonstrated that dynamic microtubule rearrangement coupled with dynein activity controls ER distribution critical for ISOC activation in PMVECs. In the present study, a retroviral construct encoding dominant negative kinesin light chain (KLCdn) was stably introduced into PAECs to reduce kinesin motor function such that microtubule bound ER would rearrange in a retrograde direction. Indeed, KLCdn expression prevented the direct activation of ISOC by Ca2+ store depletion using thapsigargin in PAECs. In addition, PAECs expressing KLCdn failed to respond to thapsigargin in forming intercellular gaps. Together these results indicate that microtubule motor function is an important determinant of ISOC activation.
- Subjects
MICROTUBULES; VASCULAR endothelium; ENDOPLASMIC reticulum; CELL membranes; ORGANELLES
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA1432
- ISSN
0892-6638
- Publication type
Article