Phosphatidylinositol 4,5-bisphosphate optical uncaging potentiates exocytosis
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Phosphatidylinositol 4,5-bisphosphate optical uncaging potentiates exocytosis
Forlagets udgivne version, 2,61 MB, PDF-dokument
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 Ca(2+) 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.
Originalsprog | Engelsk |
---|---|
Artikelnummer | e30203 |
Tidsskrift | eLife |
Vol/bind | 6 |
Antal sider | 41 |
ISSN | 2050-084X |
DOI | |
Status | Udgivet - 2017 |
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 185030190