Volume 611 Issue 7937, 24 November 2022 - Nature.com

The cover illustration shows vacuolar-type adenosine triphosphatases (V-ATPases, large blue structures) on a synaptic vesicle from a nerve cell in the mammalian brain.

V-ATPases pump protons across cellular membranes, and in neurons this process is essential for loading neurotransmitters into synaptic vesicles.

By imaging proton-pumping at the single-molecule level, the researchers were able to see that V-ATPases do not pump continuously but instead switch between three distinct modes: proton-pumping, inactive and proton-leaking.