FMP Publications

Our publications are recorded in a searchable database since 2010, updates will be added regularly.

All :: 2017
All :: (, A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, X, Y, Z 
All :: Nadler(*), Nagaraj, Nagase(*), Nagata(*), ... , Nykjaer(*) 
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Phosphatidylinositol 4,5-bisphosphate optical uncaging potentiates exocytosis
Walter(*), A. M., Müller(*), R., Tawfik(*), B., Wierda(*), K. D., Pinheiro(*), P. S., Nadler(*), A., McCarthy(*), A. W., Ziomkiewicz(*), I., Kruse(*), M., Reither(*), G., Rettig(*), J., Lehmann, M., Haucke, V., Hille(*), B., Schultz(*), C.; Sorensen(*), J. B.
Elife, 6

Tags: Molecular Pharmacology and Cell Biology (Haucke)

Abstract: Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] is essential for exocytosis. Classical ways of manipulating PI(4,5)P2 levels are slower than metabolism, making it difficult to distinguish effects of PI(4,5)P2 from those of its metabolites. We developed a membrane-permeant, photoactivatable PI(4,5)P2, which is loaded into cells in an inactive form and activated by light, allowing sub-second increases in PI(4,5)P2 levels. By combining this compound with electrophysiological measurements in mouse adrenal chromaffin cells, we show that PI(4,5)P2 uncaging potentiates exocytosis and identify synaptotagmin-1 (the Ca2+ sensor for exocytosis) and Munc13-2 (a vesicle priming protein) as the relevant effector proteins. PI(4,5)P2 activation of exocytosis did not depend on the PI(4,5)P2-binding CAPS-proteins, suggesting that PI(4,5)P2 uncaging bypasses CAPS-function. Finally, PI(4,5)P2 uncaging triggered the rapid fusion of a subset of readily-releasable vesicles, revealing a rapid role of PI(4,5)P2 in fusion triggering. Thus, optical uncaging of signaling lipids can uncover their rapid effects on cellular processes and identify lipid effectors.

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Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10
13125 Berlin, Germany
+4930 94793 - 100 
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