Pac-Man Receptor Can Be ‘Switched’ On And Off

Researchers have genetically engineered glutamate receptors to activate and deactivate on demand.

AsianScientist (Jun. 28, 2016) – What goes on inside the brain when we learn new things? Much still remains wrapped in mystery, but scientists in Japan have found a way to examine this phenomenon at the molecular level.

Researchers from Kyoto University have engineered an artificial switch that could let scientists turn individual neurotransmitter receptors on and off. Their findings, published in Nature Chemistry, could shed light on these receptors’ role in memory formation and contribute to the development of new drugs for neurological diseases such as Alzheimer’s disease.

“Investigating the functions of various neurotransmitter receptors could be immensely useful, because a majority of drugs on the market target them,” said Assistant Professor Ryou Kubota, the lead author of the study.

“But with so many similarly-structured proteins in the membrane, it’s been extremely difficult to determine which receptors do what.

“Discovering the functions of each neurotransmitter receptor in the brain could help us understand how we learn and acquire memory; to do that, it’s crucial to be able to activate them selectively.”

In the study, the team succeeded in selectively activating glutamate receptors, which are Pac-Man-shaped neutrotransmitter receptors known to be involved in memory formation.

These neurotransmitter receptors help relay information from neuron to neuron. For glutamate receptors, activation happens when they ‘bite.’ The team genetically engineered glutamate receptors to include switches that force activation and deactivation.

“The switch comes in the shape of two ‘clips’ on what would be the upper and lower lips of Pac-Man,” explained Kubota. “When we tell the clips to bind together, we force the glutamate receptor to activate.”

The current study only reports outcomes with glutamate receptors, but the authors say that their method also shows promise with other kinds of membrane receptors.

The article can be found at: Kiyonaka et al. (2016) Allosteric Activation of Membrane-Bound Glutamate Receptors Using Coordination Chemistry within Living Cells.


Source: Kyoto University.
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