Public Release: 

Scientists Bridge Gap In Cell Communication

University of Wisconsin-Madison

A critical step in communication between cells that promotes such things as bone formation, limb growth, and the development of other critical tissues, has been found by a team of researchers from the University of Wisconsin-Madison.

The discovery, reported today (July 17) in the British scientific journal Nature, while fundamental in nature, is important because it adds an essential strand of information to scientists' understanding of how cells relay molecular messages, a process that, if disrupted, can result in cancer and defects in embryonic development.

By revealing the terminus of the pathway by which cells send and receive messages, the find promises a rational basis for the future treatment of some diseases and, more immediately, gives science a new grasp of a process that triggers decisive events in cells.

Studying a well-known signaling protein called MAD, UW-Madison geneticist Allen Laughon and colleagues determined that the protein is responsible for switching genes on or off by binding directly to DNA, in effect telling the cell to start or stop a specified task.

It closes the loop, said Laughon, whose work was accomplished in fruit flies taking advantage of the well-studied process by which signaling governs wing growth. "We've shown that the MAD protein is a direct regulator of target gene transcription in response to a (specific) signal."

The mapping of the communication pathways between cells is a fundamental quest in modern biology. Identifying the messengers -- a large family of proteins that carry genetic signals and switch genes on and off -- and their roles in communicating at a distance has implications for the development of new strategies to treat diseases caused by malfunctioning genes or disrupted pathways of communication.

Communication -- or miscommunication -- between cells is the basis for many diseases. For example, in humans it is believed that there are many layers of genes which act as a group to prevent cancer by blocking the inappropriate proliferation of cells. But if these "tumor suppression genes" are defective, cells become blind to messages meant to ward off runaway cell proliferation. The result can be cancer.

"As long as cells sense this information, they don't grow out of control," Laughon said.

Now, having revealed the last leg of the communications pathway, the Wisconsin scientists have opened a window on the very root of genetically-mediated diseases like some cancers.

"We've found a mechanism that is really important," said Sean Carroll, a co-author of the study and a molecular biologist at the Howard Hughes Medical Institute at UW-Madison. "The universe of genes regulated by this pathway is very large. I would guess hundreds of genes."

"The missing link," explained Laughon, "has been how the signal switches genes on or off. This protein shuttles from the inner surface of the cell membrane right to the DNA, in one fell swoop."

The discovery, Laughon emphasized, will have no immediate medical application, but may lead to the development of new genetic-based treatments for disease. It also reveals that the pathway from cell surface to the gene is remarkably direct.

CONTACTS: Allen Laughon, (608) 262-2456, alaughon@facstaff.wisc.edu; Sean Carroll, (608) 262-6191, sbcarrol@facstaff.wisc.edu

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