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Volume 611 Issue 7937, 24 November 2022

Pump, rest, leak, repeat

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. In this week’s issue, Dimitrios Stamou and his colleagues shed light on V-ATPase dynamics in single native 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. The team suggests that this could indicate a broader biological role for ultraslow mode-switching in protein regulation.

Cover image: C. Kutzner, H. Grubmüller and R. Jahn/Max Planck Institute for Multidisciplinary Sciences; Jens Carstensen/University of Copenhagen

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