Sea skate experiment sheds light on human cell transport

Along with Mark Musch, a longtime University of Chicago collaborator, Goldstein conducted an experiment with the red blood cells of skates to understand how these skinny, graceful fish can swim from salt water to fresh water. For humans, such a drastic environmental change would prompt an equally drastic physiological change: Our cells would take in too much water, diluting blood and other body fluids and rapidly causing death. So how do skates do it?

Goldstein and Musch learned how cellular channels, or gates, spring into action when skate red blood cells become engorged with water. Vesicles, or tiny fluid-filled sacs, carry these gates up to the cell membrane. The vesicles are inserted into the membrane and a chemical process known as phosphorylation takes place. This activates the gates, which open to release excess water along with salts and other organic material.

The researchers made their discovery by using a plant-based substance to block an enzyme that causes phosphorylation. The result: The gates wouldn't open. These findings are published in the current issue of the American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, along with an accompanying editorial.

Goldstein said the results are important for a few reasons.

Because skate red blood cells closely resemble cells in the human kidney, the findings shed light on how these organs cope with excess water. But Goldstein and Musch also believe the mechanisms that trigger this cellular "release valve" are universal.

"We think that vesicle insertion, coupled with phosphorylation, is a broad mechanism for getting substances in and out of cells," Goldstein said. "The idea that we can apply this knowledge to other cells and other animals – including humans – is what makes the findings exciting."

In type 1 diabetes, cells lose their ability to transport glucose. Goldstein and Musch say their findings could explain the problem. People with type 1 diabetes don't produce insulin. Without that hormone, vesicles aren't inserted into cell membranes – and glucose can't be moved between cells.

And when channels are blocked, damaged cells can't die. This cell "suicide" is one of the body's defenses against cancer. "There is a possible relationship between operation of these channels and the uncontrolled multiplication of cancer cells," Goldstein said. "If so, this research points up an important area for future research."

Source : Brown University