Vesicular ATP transport is a hard (V)NUT to crack

ATP has been known for decades as a major form of molecular energy currency, generated by glycolysis, respiration, or other reactions, and used to provide energy for a myriad of other biochemical processes. However, in recent years it has become apparent that ATP also fulfills a role as an extracellular signaling molecule. ATP is secreted by fusion of ATP-containing intracellular vesicles with the cell membrane, but the machinery responsible for filling these vesicles has, until now, been a mystery. In a recent issue of PNAS, Yoshinori Moriyama and his coworkers at Okayama University have identified an ATP transporter present in secretory vesicles that fulfills all of the requirements of the elusive vesicular ATP transporter, which they have named VNUT (1).

When a nerve cell sends a signal to an adjacent cell, that signal is almost always a chemical neurotransmitter secreted by a process known as exocytosis. Neurons contain small intracellular compartments, called synaptic vesicles, filled with a neurotransmitter such as serotonin, acetylcholine, or glutamate. When these vesicles fuse with the cell membrane, their contents are released from the cell and are free to activate receptors on the surface of neighboring cells. Researchers have known for many years that along with the neurotransmitter, ATP is also released, and that most synaptic vesicles store this nucleotide, which is also used to power many of the cell's energy-dependent reactions (2). Until now, however, the history of research on ATP storage within synaptic vesicles had been problematic, leading skeptics to doubt that any firm conclusions could be drawn (3). In this novel and incisive series of experiments, Moriyama and coworkers (1) have finally banished the demons of ATP transport by unequivocally demonstrating the transporter's activity in a purified and reconstituted preparation.

ATP was generally recognized to constitute a major portion of the contents …

*E-mail: gary.rudnick{at}yale.edu