By tracking the flow of information in a cell preparing to split, Johns Hopkins scientists have identified a protein mechanism that coordinates and regulates the dynamics of shape change necessary for division of a single cell into two daughter cells.
The protein, called 14-3-3, sits at an intersection where it integrates converging signals from within the cell and cues cell shape change and, ultimately, the splitting that allows for normal and abnormal cell growth, such as in tumors.
In a report published Nov. 9 in Current Biology, the Hopkins team links 14-3-3 directly to myosin II, a complex of motor proteins that monitors and smoothes out the shape changes to ensure accurate division.
"The discovery of this role for 14-3-3 has immediate and important medical implications because cell division already is one of the major targets of anticancer drugs," says Douglas Robinson, Ph.D., an associate professor of cell biology at the Johns Hopkins School of Medicine. "This protein provides a new opportunity for tweaking the cell division system."
The new findings grew out of studies of the so-called mitotic spindle in the one-celled amoeba Dictyostelium. The spindle's job is to separate all the genetic material into two identical sets, one for each daughter cell, and coordinate cell division activities at the cell's outer membrane.
Using a painstaking chemical-genetic approach, the scientists altered the cells so that they grew only half as well as normal. They then used tools of genetic engineering to try to make the cells grow normally again.
Specifically, they used a chemical that makes the spindles fall apart, and then they searched for genes "turned on" in response to this catastrophe. Out popped 14-3-3. When they increased production of 14-3-3, they found that the chemical lost its damaging effect.
Next, they blocked 14-3-3 and noticed traits in these cells reminiscent of what h
|Contact: Maryalice Yakutchik|
Johns Hopkins Medical Institutions