| Autor: |
Claire A. Ruddiman, Richard Peckham, Melissa A. Luse, Yen-Lin Chen, Maniselvan Kuppusamy, Bruce Corliss, P. Jordan Hall, Chien-Jung Lin, Shayn M Peirce, Swapnil K. Sonkusare, Robert P. Mecham, Jessica E. Wagenseil, Brant E. Isakson |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.08.01.502310 |
| Popis: |
In the resistance artery endothelium, we show phosphatidylserine (PS) localizes to a specific subpopulation of myoendothelial junctions (MEJs), signaling microdomains that regulate vasodilation. In silico data has implied PS may compete with PIP2 binding on Kir2.1, a channel involved in vasodilatory signaling. We found 83.33% of Kir2.1-MEJs also contained PS, possibly indicating an interaction where PS regulates Kir2.1. Electrophysiology experiments on HEK cells demonstrate PS blocks PIP2 activation of Kir2.1, and addition of exogenous PS blocks PIP2-mediated Kir2.1 vasodilation in resistance arteries. Using a mouse model lacking canonical MEJs in resistance arteries (Elnfl/fl/Cdh5-Cre), PS localization in endothelium was disrupted and PIP2 activation of Kir2.1 was significantly increased. Taken together, our data suggests PS enrichment to MEJs inhibits PIP2-mediated activation of Kir2.1 to tightly regulate changes in arterial diameter, and demonstrates the intracellular lipid localization within endothelium is an important determinant of vascular function. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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