Optogenetic acidification of synaptic vesicles and lysosomes

Rost, Benjamin R and Schneider, Franziska and Grauel, M Katharina and Wozny, Christian and G Bentz, Claudia and Blessing, Anja and Rosenmund, Tanja and Jentsch, Thomas J and Schmitz, Dietmar and Hegemann, Peter and Rosenmund, Christian (2015) Optogenetic acidification of synaptic vesicles and lysosomes. Nature Neuroscience, 18 (12). pp. 1845-1852. ISSN 1097-6256

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    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.