Exclusive photorelease of signalling lipids at the plasma membrane

André Nadler, Dmytro A. Yushchenko, Rainer Müller, Frank Stein, Suihan Feng, Christophe Mulle, Mario Carta, Carsten Schultz

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32 Scopus citations

Abstract

Photoactivation of caged biomolecules has become a powerful approach to study cellular signalling events. Here we report a method for anchoring and uncaging biomolecules exclusively at the outer leaflet of the plasma membrane by employing a photocleavable, sulfonated coumarin derivative. The novel caging group allows quantifying the reaction progress and efficiency of uncaging reactions in a live-cell microscopy setup, thereby greatly improving the control of uncaging experiments. We synthesized arachidonic acid derivatives bearing the new negatively charged or a neutral, membrane-permeant coumarin caging group to locally induce signalling either at the plasma membrane or on internal membranes in β-cells and brain slices derived from C57B1/6 mice. Uncaging at the plasma membrane triggers a strong enhancement of calcium oscillations in β-cells and a pronounced potentiation of synaptic transmission while uncaging inside cells blocks calcium oscillations in β-cells and causes a more transient effect on neuronal transmission, respectively. The precise subcellular site of arachidonic acid release is therefore crucial for signalling outcome in two independent systems.

Original languageEnglish (US)
Article number10056
JournalNature Communications
Volume6
DOIs
StatePublished - Dec 21 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Nadler, A., Yushchenko, D. A., Müller, R., Stein, F., Feng, S., Mulle, C., Carta, M., & Schultz, C. (2015). Exclusive photorelease of signalling lipids at the plasma membrane. Nature Communications, 6, [10056]. https://doi.org/10.1038/ncomms10056