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Nat Neurosci. 2015 Dec;18(12):1845-1852. doi: 10.1038/nn.4161. Epub 2015 Nov 9.

Optogenetic acidification of synaptic vesicles and lysosomes.

Author information

1
Neuroscience Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
2
German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
3
Institute of Biology, Experimental Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
4
Current address: National Heart and Lung Institute, Imperial College London, United Kingdom.
5
University of Strathclyde, Glasgow, UK.
6
Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany.
7
Leibniz-Institut für Molekulare Pharmakologie (FMP), Berlin, Germany.
#
Contributed equally

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.

PMID:
26551543
PMCID:
PMC4869830
DOI:
10.1038/nn.4161
[Indexed for MEDLINE]
Free PMC Article

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