CELLULAR BIOLOGY
Mechanism believed found that regulates movement within cells

Jim Barlow, Life Sciences Editor
(217) 333-5802; b-james3@uiuc.edu

9/1/2001

Photo by Bill Wiegand Vladimir I. Gelfand, a professor of cell and structural biology, says that If the mechanism he and his research team indentified is indeed common, new drugs potentially could target it to stop the replication of cancer-laden cells.

CHAMPAIGN, Ill. — The movement of pigment along roadway-like tracks in skin cells dictates the changing colors of frogs, fish and many other animals. To biologists looking beyond the color-shifting process, however, a more fundamental mechanism involved in cell division has come into view.

In the Aug. 17 issue of Science, researchers say they have identified a mechanism that determines whether a pigment moves or not. A small regulatory protein, they say, determines if a part of the tail of a larger motor protein binds to a pigment, allowing it to move. The study shows that the motor disengages as a result of phosphorylation, a chemical reaction occurring in cell division.

The discovery was made in pigment cells taken from the skin of a frog (Xenopus), but the evidence suggests that the tail phosphorylation may be common in many other cells.

"We want to believe that what we have found is a universal mechanism that regulates movement within the cell," said Vladimir I. Gelfand, a professor of cell and structural biology at the University of Illinois. If the mechanism is indeed common, he said, new drugs potentially could target it to stop the replication of cancer-laden cells.

Pigment is a form of an organelle. Organelles are structures having a variety of duties within cells. Motor proteins, activated by hormones, drive organelles along two cytoskeletal systems comparable to interstates and narrow city streets. During cell division, the organelles are stopped so they do not interfere and to assure the proper distribution of genetic material.

Gelfand, in the Journal of Cell Biology in 1999, had identified myosin-V as the motor protein that moves organelles along the city-like roads made up of actin filaments. Two other motor proteins do the job along microtubules, or larger, longer-reaching, interstate-like fibers.

The new study details the binding of myosin-V to pigment organelles. "We found that when the motor is on, it is sitting on the organelle," Gelfand said. "When the motor is off, there is nothing there. The motor is in neutral, as if a clutch is pushed. We wanted to know why the motor disengages."

The answer was the smaller protein, known as calcium/calmodulin-dependent protein kinase II (CaMKII). A series of experiments clearly showed that CaMKII is the clutch in a variety of scenarios involving myosin-V, Gelfand said. The two proteins are often found together in laboratory analyses.

"It is possible that CaMKII regulates myosin-V functions in neurons with the same basic mechanism that is described here for pigment cells," the researchers wrote in their conclusion.

The Science paper was written by Gelfand and two UI graduate students, Ryan L. Karcher and Joseph T. Roland, Stephen A. Carr of Millennium Pharmaceuticals and Francesca Zappacosta, Michael J. Huddleston and Roland S. Annan, all of GlaxoSmithKline. The National Science Foundation and National Institutes of Health funded the research.