Cholesterol, often condemned for its role in heart disease, has always been known to be essential for the health of the fatty membranes that surround individual cells.
New research at UT Southwestern Medical Center has discovered a novel role for cholesterol inside the cell itself – anchoring a signaling pathway linked to cell division and cancer. Dr. Richard G.W. Anderson, chairman of cell biology and senior author of the study says cell signals have to be tightly controlled and if the signaling machines do not work, which happens when the cell hasn't enough cholesterol, the cell gets the wrong information, and disease results."
The fluid cell membrane, contains cholesterol and this research focuses on regions of the membrane where cholesterol is enriched. These regions, called lipid domains, are more rigid than the rest of the cell membrane because of cholesterol and play a critical role in organizing signaling machinery at the cell surface. The correct arrangement of signaling modules in these domains is vital for communication inside the cell and is dependent on proper levels of cholesterol.
While looking at how cholesterol moves to the membrane to get to lipid domains, the team found that it could also work outside the membrane to regulate a vital signaling pathway that occurs inside the cell. By interacting with a protein called the oxysterol binding protein (OSBP), cholesterol bands together a group of enzymes that deactivates extracellular signal-related kinase (ERK). Overactive ERK is associated with many cancers.
When the level of cholesterol in lipid domains is normal, the OSBP-cholesterol complex keeps the amount of active ERK under control. When cholesterol in the domains gets too low, however, the complex falls apart, leading to abnormally high levels of active ERK.