Optogenetic acidification of synaptic vesicles and lysosomes

Benjamin R Rost, Franziska Schneider, M Katharina Grauel, Christian Wozny, Claudia G Bentz, Anja Blessing, Tanja Rosenmund, Thomas J Jentsch, Dietmar Schmitz, Peter Hegemann, Christian Rosenmund

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Acidification is required for the function of many intracellular organelles, but methods to acutely manipulate their intraluminal pH have not been available. Here we present a targeting strategy to selectively express the light-driven proton pump Arch3 on synaptic vesicles. Our new tool, pHoenix, can functionally replace endogenous proton pumps, enabling optogenetic control of vesicular acidification and neurotransmitter accumulation. Under physiological conditions, glutamatergic vesicles are nearly full, as additional vesicle acidification with pHoenix only slightly increased the quantal size. By contrast, we found that incompletely filled vesicles exhibited a lower release probability than full vesicles, suggesting preferential exocytosis of vesicles with high transmitter content. Our subcellular targeting approach can be transferred to other organelles, as demonstrated for a pHoenix variant that allows light-activated acidification of lysosomes.

LanguageEnglish
Pages1845-1852
Number of pages8
JournalNature Neuroscience
Volume18
Issue number12
DOIs
Publication statusPublished - 9 Nov 2015

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Optogenetics
Proton Pumps
Synaptic Vesicles
Lysosomes
Organelles
Light
Exocytosis
Neurotransmitter Agents

Keywords

  • endocytosis
  • optogenetics
  • neurotransmitters
  • transporters in the nervous system

Cite this

Rost, B. R., Schneider, F., Grauel, M. K., Wozny, C., G Bentz, C., Blessing, A., ... Rosenmund, C. (2015). Optogenetic acidification of synaptic vesicles and lysosomes. Nature Neuroscience, 18(12), 1845-1852. https://doi.org/10.1038/nn.4161
Rost, Benjamin R ; Schneider, Franziska ; Grauel, M Katharina ; Wozny, Christian ; G Bentz, Claudia ; Blessing, Anja ; Rosenmund, Tanja ; Jentsch, Thomas J ; Schmitz, Dietmar ; Hegemann, Peter ; Rosenmund, Christian. / Optogenetic acidification of synaptic vesicles and lysosomes. In: Nature Neuroscience. 2015 ; Vol. 18, No. 12. pp. 1845-1852.
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Rost, BR, Schneider, F, Grauel, MK, Wozny, C, G Bentz, C, Blessing, A, Rosenmund, T, Jentsch, TJ, Schmitz, D, Hegemann, P & Rosenmund, C 2015, 'Optogenetic acidification of synaptic vesicles and lysosomes' Nature Neuroscience, vol. 18, no. 12, pp. 1845-1852. https://doi.org/10.1038/nn.4161

Optogenetic acidification of synaptic vesicles and lysosomes. / Rost, Benjamin R; Schneider, Franziska; Grauel, M Katharina; Wozny, Christian; G Bentz, Claudia; Blessing, Anja; Rosenmund, Tanja; Jentsch, Thomas J; Schmitz, Dietmar; Hegemann, Peter; Rosenmund, Christian.

In: Nature Neuroscience, Vol. 18, No. 12, 09.11.2015, p. 1845-1852.

Research output: Contribution to journalArticle

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Rost BR, Schneider F, Grauel MK, Wozny C, G Bentz C, Blessing A et al. Optogenetic acidification of synaptic vesicles and lysosomes. Nature Neuroscience. 2015 Nov 9;18(12):1845-1852. https://doi.org/10.1038/nn.4161