Cells rely on calcium as a universal means of communication. For example, a sudden rush of calcium can trigger nerve cells to convey thoughts in the brain or cause a heart cell to beat. A longstanding mystery has been how cells and molecules manage to appropriately sense and respond to the variety of calcium fluctuations within cells.
Reporting in the June 27 issue of Cell, a team of biomedical engineers at the Johns Hopkins School of Medicine has discovered how the calcium sensor protein calmodulin can gauge both the local flow of calcium, in through the closest channel, as well as the global calcium flow entering the many channels across the entire cell.
"It's like being at a cocktail party where the easiest person to listen to is the one closest to you, but we all have the ability to keep an ear out for other interesting conversations going on throughout the room," says David Yue, M.D., Ph.D., a professor of biomedical engineering at Hopkins. "It turns out that calmodulin is doing a similar thing, sensing the calcium coming through the closest channel through one ear while the other ear 'listens' to the calcium coming through distant channels across the cell."
Normally, calmodulin is positioned right near each calcium channel. Several years ago, scientists discovered that calmodulin somehow can switch its sensory focus between local calcium and global calcium entering the cell through channels at a distance.
The calmodulin protein, explains Yue, is made of two ball-like lobes, and it's these two lobes that act as the different calcium-sensing "ears." The C lobe listens locally and the N lobe listens globally, across the whole cell. To figure out how calmodulin's two lobes can sense different sources of calcium, the team took a two-pronged approach.
First, they used computers to perform mathematical simulations that tested different potential calcium detection mechanisms of the calmodulin lobes. Others
|Contact: Maryalice Yakutchik|
Johns Hopkins Medical Institutions