Mysteries of the brain: how V-ATPase enzyme takes ‘breaks’

A study published in Nature revealed that an enzyme, V-ATPase, randomly switches on and off in the brain. V-ATPase provides energy for neurotransmitters, allowing signal transmission between neurons and thus contributes to neuron-neuron communication. This study opens avenues to understand the brain in detail and develop new therapeutics.

“This is the first time anyone has studied these mammalian brain enzymes one molecule at a time, and we are awed by the result,” says Professor Dimitrios Stamou, the lead author of the study from the department of chemistry at the University of Copenhagen, in a statement.

The V-ATPase enzyme is abundant in the body and helps in essential biological functions and in the brain, it specifically influences the neurotransmitter function.

“This is the first time anyone has studied these mammalian brain enzymes one molecule at a time, and we are awed by the result”- Prof Stamou

Energising the connection

Communication among the neurons is an essential process in the brain in response to any activity, adaptation, or learning of new things. This happens via the transfer of neurotransmitters between neurons. Studies have shown that neurons branch out into extensions called dendrites that help transmit the signal in the brain. Each of these dendrites has spoon-shaped structures called synaptic vesicles that act as containers to hold neurotransmitters.

Dr Anju Tripathi, research associate at Meharry Medical College, USA, who was not connected with the research, says that V-ATPase acts like a pump to transfer information between neurons. “It first pushes the neurotransmitter into the vesicle and then releases it into the synapse (junction between two neurons),” he explains.

Until now, researchers believed that this enzyme is always active in the neurons to carry out this signal transfer. However, the Copenhagen study found that V-ATPase randomly deactivates for minutes to hours, yet the human brain appears to function very well. In addition, the researchers also found that each synaptic vesicle contains only one V-ATPase molecule, contrary to the previous belief of multiple molecules.

Ready-go-rest

The researchers conducted experiments on the brain cells of rats to observe how V-ATPase functions and observed that it works in three modes:

• Ready to transfer mode: the molecule is partially active and energised but does not transfer the energy to the neurotransmitter.
• Active mode: the molecule transfers energy to the neurotransmitter to release it from the vesicle and communicate the signal.
• Resting phase: the molecule is in the off mode, doing nothing.

“It is nearly incomprehensible that the extremely critical process of loading neurotransmitters in containers is delegated to only one molecule per container. Especially when we find that 40% of the time, these molecules are switched off,” says Stamou.

Dr Tripathi says, “Professor Stamou’s research finding has changed the understanding of neuron communication in mammals.” Further investigations of the enzyme’s functions could lead to therapeutics for neurological disorders, he adds.