Biological complexity: brain receptor in action (Introduction)

by David Turell , Monday, July 24, 2017, 21:12 (2679 days ago) @ David Turell

A highly complex molecule opens a pore like a camera shutter to allow ions to move creating the connecting synapses to occur and transmit impulses:

https://medicalxpress.com/news/2017-07-scientists-capture-image-major-brain.html

"Columbia University Medical Center (CUMC) researchers have captured the first three-dimensional snapshots of the AMPA-subtype glutamate receptor in action. The receptor, which regulates most electrical signaling in the brain, is involved in several important brain activities, including memory and learning.

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"'With our new findings, we can now, for the first time, visualize how the neurotransmitter glutamate opens glutamate receptor ion channels," said Alexander Sobolevsky, PhD, associate professor of biochemistry and molecular biophysics at Columbia and senior author of the paper. "This is the fundamental process that directly affects learning and memory.

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"Most signaling in the brain is triggered by glutamate, a neurotransmitter that activates proteins on the surface of neurons called glutamate receptors. Glutamate receptors underlie a variety of high cognitive functions, including learning and memory. AMPA receptors are glutamate receptors that open and close very quickly—in less than a millisecond—and are involved in fast processes in the brain, such as the rapid perception and reaction of an organism to its surrounding environment.

"Previously, the Sobolevsky lab deciphered the structures of the AMPA receptor alone and in complex with other proteins that regulate the speed and strength of synaptic connections. In the current study, the researchers captured the AMPA receptor in action, as glutamate activates the receptor to allow ions to flow through its channel and initiate signaling in the brain. This provides the first precise insights into how receptors mediate brain function.

"To freeze the AMPA receptor in an active state, the researchers fused it with stargazin, a regulatory protein that prompts the channel to open. The images they captured show that when signaling molecules such as glutamate are present, the entrance to the AMPA receptor, which consists of four units, opens up like a camera's iris, or aperture, to reveal its pore. To shepherd the ions through, the receptor widens the diameter of its channel, and a specialized channel pore lining ushers the ions into the cell.

"'These new fundamental discoveries have implications for our understanding of neurotransmission by glutamate, our brain's major neurotransmitter" says Edward C. Twomey, a PhD candidate at CUMC and first author of the paper. "Understanding these processes will impact future studies on glutamate receptor signaling in neurodegenerative diseases as well as drug design.'"

Comment: be sure to look at the article to see models of the molecule, made up of thousands of amino acids in an exact order and folding for proper function. This complexity is not by chance!