DALLAS March 3, 2005 Cholesterol, often stigmatized for its role in heart disease, has long been known to be essential for the health of the fat-laden membranes that surround individual cells. New findings by researchers at UT Southwestern Medical Center highlight a novel role for cholesterol inside the cell itself anchoring a signaling pathway linked to cell division and cancer.

These findings appear in the March 4 issue of Science and are available online.

"Cell signals have to be tightly controlled," said Dr. Richard G.W. Anderson, chairman of cell biology and senior author of the study. "If the signaling machines do not work, which can happen when the cell doesn't have enough cholesterol, the cell gets the wrong information, and disease results."

The cell membrane, which is fluid in nature, contains cholesterol. Dr. Anderson's 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 studying how cholesterol moves to the membrane to get to lipid domains, Dr. Anderson, who holds the Cecil H. Green Distinguished Chair in Cellular and Molecular Biology, and colleagues found that cholesterol can work outside the membrane to regulate a key signaling pathway that occurs inside the cell. Through an interaction with a protein called the oxysterol binding protein (OSBP), cholesterol holds together a group of enzymes that deactivates extracellular signal-related kinase (ERK). Overactive ERK is associated with multiple cancers.

When the amount of cholesterol in lipid domains is normal, the OSBP-cholesterol complex keeps the amount of active ERK under control. When choles
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Contact: Megha Satyanarayana
megha.saty@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
3-Mar-2005

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