Molecular Motor Shuttles Key Protein In Response To Light
In experiments with fruit flies, Johns Hopkins researchers have discovered how a key light-detecting molecule in the eye moves in response to changes in light intensity.
Their finding adds to growing evidence that some creatures -- and probably people -- adapt to light not only by mechanically shrinking the pupil to physically limit how much light enters the eye, but also by a chemical response.
Building on their previous work showing that specific proteins in eye cells are redistributed in response to bright light, the Johns Hopkins team now reports how a key protein called arrestin is shuttled from a "holding area" where it binds and calms a light-detecting protein. Writing in the July 7 issue of Neuron, the team says arrestin is moved around by a tiny molecular motor, called myosin, which travels along the "train tracks" of the cell's internal skeleton.
Arrestin's swift relocation, the researchers proposed, helps prevent temporary blindness that would otherwise be caused by a sudden increase in light intensity, such as occurs when stepping from a dark movie theater into the bright afternoon sunshine.
"We knew that arrestin was transported, but we didn't know how this occurred," says Craig Montell, Ph.D., professor of biological chemistry. "Fly and mammalian eyes have similar light detector cells and proteins, and it takes about the same amount of time for our eyes to adapt to light, so we suspect that comparable mechanisms exist in humans."
The light-detecting cells in fruit flies are similar to the rod and cone cells found in the human retina. One end of each cell contains the protein that directly responds to light, but other proteins critical for the light response are shifted back and forth into different parts of the cell in a light-dependent manner. Scientists didn't know how these molecules might be moved from one end of the cell to the other, until now.
Postdoctoral fellow Seung-Jae Lee, Ph.D., had a hunch that myosin -- a molecular motor -- might play a role in transporting arrestin. Studying flies that had been engineered to lack a myosin, dubbed NINAC for "neither inactivation nor afterpotential C," Lee found that arrestin didn't move when the fly was exposed to bright light. Instead, arrestin stayed in the protein-making part of the cell.
"For the cell to properly adapt to bright light, arrestin needs to move," says Montell. "If it doesn't, the cell remains as sensitive to light as it was when it was dark."
While some details of arrestin's shuttling in flies are still unclear, the researchers showed that arrestin and the motor don't bind to each other directly. Instead, they are "glued" together by a sticky fat, called phosphoinositides.
"Arrestin is pasted onto the myosin motor and is quickly taken to its target destination within the cell," says Montell. "This explains why it moves much faster than if it just moved passively, essentially wandering to the other side of the cell."
The researchers will now study mice to see if there are similar chemical controls of light adaptation. They will also start examining other proteins that move in response to light in both flies and mice.
The research was supported by the National Eye Institute. Authors on the paper are Lee and Montell. Lee is now a postdoctoral fellow in the Department of Biochemistry and Biophysics at the University of California, San Francisco.
Source: Johns Hopkins Medical Institutions. July 2004.
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