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2015 ; 18
(12
): 1845-1852
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Optogenetic acidification of synaptic vesicles and lysosomes
#MMPMID26551543
Rost BR
; Schneider F
; Grauel MK
; Wozny C
; Bentz C
; Blessing A
; Rosenmund T
; Jentsch TJ
; Schmitz D
; Hegemann P
; Rosenmund C
Nat Neurosci
2015[Dec]; 18
(12
): 1845-1852
PMID26551543
show ga
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.