Microtubule Motors Regulate ISOC Activation Necessary to Increase Endothelial Cell Permeability.

Microtubule Motors Regulate ISOC Activation Necessary to Increase Endothelial Cell Permeability. Research Abstract Details 

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Microtubule Motors Regulate ISOC Activation Necessary to Increase Endothelial Cell Permeability. Abstract Text:

Songwei Wu,Hairu Chen,Mikhail F Alexeyev,Judy A C King,Timothy M Moore,Troy Stevens,Ronald D Balczon,Songwei Wu,Hairu Chen,Mikhail F Alexeyev,Judy A C King,Timothy M Moore,Troy Stevens,Ronald D Balczon,Songwei Wu,Hairu Chen,Mikhail F Alexeyev,Judy A C King,Timothy M Moore,Troy Stevens,Ronald D Balczon,

Calcium store depletion activates multiple ion channels, including calcium-selective and nonselective channels. Endothelial cells express TRPC1 and TRPC4 proteins that contribute to a calcium-selective store-operated current, I(SOC). Whereas thapsigargin activates the I(SOC) in pulmonary artery endothelial cells (PAECs), it does not activate I(SOC) in pulmonary microvascular endothelial cells (PMVECs), despite inducing a significant rise in global cytosolic calcium. Endoplasmic reticulum exhibits retrograde distribution in PMVECs when compared with PAECs. We therefore sought to determine whether endoplasmic reticulum-to-plasma membrane coupling represents an important determinant of I(SOC) activation in PAECs and PMVECs. Endoplasmic reticulum organization is controlled by microtubules, because nocodozole induced microtubule disassembly and caused retrograde endoplasmic reticulum collapse in PMVECs. In PMVECs, rolipram treatment produced anterograde endoplasmic reticulum distribution and revealed a thapsigargin-activated I(SOC) that was abolished by nocodozole and taxol. Microtubule motors control organelle distribution along microtubule tracks, with the dynein motor causing retrograde movement and the kinesin motor causing anterograde movement. Dynamitin expression reduces dynein motor function inducing anterograde endoplasmic reticulum transport, which allows for direct activation of I(SOC) by thapsigargin in PMVECs. In contrast, expression of dominant negative kinesin light chain reduces kinesin motor function and induces retrograde endoplasmic reticulum transport; dominant negative kinesin light chain expression prevented the direct activation of I(SOC) by thapsigargin in PAECs. I(SOC) activation is an important step leading to disruption of cell-cell adhesion and increased macromolecular permeability. Thus, microtubule motor function plays an essential role in activating cytosolic calcium transitions through the membrane I(SOC) channel leading to endothelial barrier disruption.

Microtubule Motors Regulate ISOC Activation Necessary to Increase Endothelial Cell Permeability. Publishing Authors By Initials

S Wu,H Chen,MF Alexeyev,JA King,TM Moore,T Stevens,RD Balczon,S Wu,H Chen,MF Alexeyev,JA King,TM Moore,T Stevens,RD Balczon,S Wu,H Chen,MF Alexeyev,JA King,TM Moore,T Stevens,RD Balczon,

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Microtubule Motors Regulate ISOC Activation Necessary to Increase Endothelial Cell Permeability. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 34801-8

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 4

MONTH: 10

YEAR: 2007

Microtubule Motors Regulate ISOC Activation Necessary to Increase Endothelial Cell Permeability. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

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AFFILIATION: Departments of Molecular and Cellular Pharmacology, Cell Biology and Neuroscience, Pathology, and Medicine.

Country: United States

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MEDLINETA: J Biol Chem

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