SAN FRANCISCO, July 4 (Xinhua) -- Researchers with the University of California, San Francisco, have mapped in detail a protein complex called NOMPC, which acts as a "mechanoreceptor" in animals from fruit flies to fish and frogs, and is tasked to detect cells' motion to produce senses of touch and hearing.
The structure, reported in a recent issue of the journal Nature, reveals a machine that depends on a quartet of tiny springs that tether the complex to the cell's "skeleton" and react to its movement.
As senses go, each relies on "receptor" molecules that turn signals like light, sound, and movement into electrical impulses for nerves to carry to the brain. Researchers have a fairly complete understanding of how receptors in the eye translate light into sight, and they've mapped many of the proteins in the nose and mouth that translate chemical signals into smell and taste.
However, the mechanoreceptors are still mysterious.
The NOMPC receptor in the new study, which is not found in mammals, was mapped in such detail thanks to recent technological breakthroughs in a technique known as single particle electron cryo-microscopy. Using this technique, the NOMPC receptor was revealed as a bundle of four identical proteins that sits in a cell's membrane, each with a spring-like tether reaching into the cell.
Previous experiments in the lab of Yuh Nung Jan, a senior author on the study and professor of physiology at UCSF, have shown that the receptor does not respond to movements in the membrane alone, but that larger movements in the cytoskeleton, the network of structural fibers that allow the cell to hold its shape, cause bundle to open up, forming a hole in the cell's membrane. Charged ions rush through the hole into the cell, creating an electrical impulse that signals touch to the nervous system.
And previously mapped touch receptors float free in the cell membrane, responding only when their particular patch of the cell's surface changes shape.
The new structural data show how NOMPC's spring-like tethers might tie it to the cytoskeleton, potentially enabling the receptor to sense distant changes in the cell's shape. "This is the first tethered receptor to be modeled in such detail," Peng Jin, a postdoc in the Jan lab and one of the lead authors on the study, was quoted as saying in a news release. "We were surprised to see that nature has created its own tiny spring to tie the receptor to the cytoskeleton."
To fully understand how channels like NOMPC open and close, researchers must observe the structure of the channels in both open and closed states. And the proteins that coordinate the mechanical senses, like touch and hearing, must be directly pulled or twisted open by microscopic forces. "It's difficult to apply a directional force to all these individual molecules," said David Bulkley, the other lead author on the study. "And we don't know which direction will activate the channel -- do you pull it, do you push it, do you twist it?"
To work around this problem, the researchers are looking to find ways to force the channel open, perhaps by finding a molecule that binds to and locks open the protein, or by producing mutant versions of the protein which are stuck in the "open" position.