Cholesterol Plays Key Role In Cell Signaling
Principal investigator Wonhwa Cho, professor of chemistry at the University of Illinois at Chicago, and colleagues, write about their discovery in a paper published earlier in December in the journal Nature Communications.
Usually, news about cholesterol tends to focus on its role in heart disease, as a result of which it has acquired somewhat of a bad reputation. But cholesterol is an essential component of healthy cells.
Until recently, however, because it is found sandwiched between the inner and outer surfaces of cell membranes, cell biologists thought cholesterol's main work was confined to interactions with other molecules in the membrane.
For instance, in 2011, a team of scientists at the National Institute of Standards and Technology (NIST) and University of California, Irvine, using neutron diffraction, revealed how cholesterol helped to "maintain order" within the cell membrane.
But Cho and colleagues have discovered cholesterol also appears to interact with proteins in the interior of the cell.
In this latest study, they reveal how cholesterol interacts with a scaffold protein. A scaffold protein uses its physical structure to bring together other proteins so they can pass signals to each other. They have protein binding sites that offer the signaling proteins a place to latch onto.
The authors found that cholesterol binds to a region on the scaffold protein where one of its signaling partners also binds. And they discovered that disruption of the cholesterol binding to that site also stopped the partner from activating.
"Here we show that cholesterol specifically binds many PDZ domains found in scaffold proteins, including the N-terminal PDZ domain of NHERF1/EBP50 ... Disruption of the cholesterol-binding activity of NHERF1 largely abrogates its dynamic co-localization with and activation of cystic fibrosis transmembrane conductance regulator, one of its binding partners in the plasma membrane of mammalian cells," they write.
In their paper, they give a detailed description of how the scaffold protein attaches itself to the membrane and reaches into it to find and bind the cholesterol.
The team suggests this way of interacting with cholesterol could be used by many proteins inside cells and sheds light on the importance of cholesterol to healthy cell functioning.
Cho says much of the existing data on how cholesterol behaves in cell processes has been difficult to interpret. He says their discovery is important because it "will help people understand how cholesterol may regulate other cellular processes".
Written by Catharine Paddock PhD