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• W2036402933 endingPage "14508" @default.
• W2036402933 startingPage "14503" @default.
• W2036402933 abstract "Ca 2+ is considered a key element in multiple steps during regulated exocytosis. During the postfusion phase, an elevated cytoplasmic Ca 2+ concentration ([Ca 2+ ]) c leads to fusion pore dilation. In neurons and neuroendocrine cells, this results from activation of voltage-gated Ca 2+ channels in the plasma membrane. However, these channels are activated in the prefusion stage, and little is known about Ca 2+ entry mechanisms during the postfusion stage. This may be particularly important for slow and nonexcitable secretory cells. We recently described a “fusion-activated“ Ca 2+ entry (FACE) mechanism in alveolar type II (ATII) epithelial cells. FACE follows initial fusion pore opening with a delay of 200–500 ms. The site, molecular mechanisms, and functions of this mechanism remain unknown, however. Here we show that vesicle-associated Ca 2+ channels mediate FACE. Using RT-PCR, Western blot analysis, and immunofluorescence, we demonstrate that P2X 4 receptors are expressed on exocytotic vesicles known as lamellar bodies (LBs). Electrophysiological, pharmacological, and genetic data confirm that FACE is mediated via these vesicular P2X 4 receptors. Furthermore, analysis of fluorophore diffusion into and out of individual vesicles after exocytotic fusion provides evidence that FACE regulates postfusion events of LB exocytosis via P2X 4 . Fusion pore dilation was clearly correlated with the amplitude of FACE, and content release from fused LBs was accelerated in fusions followed by FACE. Based on these findings, we propose a model for regulation of the exocytotic postfusion phase in nonexcitable cells in which Ca 2+ influx via vesicular Ca 2+ channels regulates fusion pore expansion and vesicle content release." @default.
• W2036402933 created "2016-06-24" @default.
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• W2036402933 date "2011-08-15" @default.
• W2036402933 modified "2023-10-01" @default.
• W2036402933 title "Fusion-activated Ca ²⁺ entry via vesicular P2X ₄ receptors promotes fusion pore opening and exocytotic content release in pneumocytes" @default.
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• W2036402933 doi "https://doi.org/10.1073/pnas.1101039108" @default.
• W2036402933 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3167537" @default.
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• W2036402933 hasPublicationYear "2011" @default.
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