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Optogenetic acidification of synaptic vesicles and lysosomes

Official URL:https://doi.org/10.1038/nn.4161
PubMed:View item in PubMed
Creators Name:Rost, B.R. and Schneider, F. and Grauel, M.K. and Wozny, C. and Bentz, C.G. and Blessing, A. and Rosenmund, T. and Jentsch, T.J. and Schmitz, D. and Hegemann, P. and Rosenmund, C.
Journal Title:Nature Neuroscience
Journal Abbreviation:Nat Neurosci
Volume:18
Number:12
Page Range:1845-1852
Date:December 2015
Keywords:Endocytosis, Neurotransmitters, Optogenetics, Transporters In The Nervous System, Animals, Mice, Rats
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.
ISSN:1097-6256
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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