Cholesterol Anchor Helps Signaling Proteins Direct Development

A quirky genius of the protein family has sprung another surprise on scientists, and its newest stunt has revealed that cholesterol, often villified for its role in heart disease, actually wears a white hat during the earliest stages of life.

In this week's Science, Johns Hopkins and Howard Hughes Medical Institute scientists report that hedgehog proteins, an unusual group of proteins that help shape many features of a developing embryo, pick up molecules of cholesterol to facilitate their work.

Researchers have long known that completely suppressing cholesterol production leads to birth defects in animals; the new work suggests that this may be because lack of cholesterol interferes with the production of hedgehog protein or with the way it spreads through tissues.

"While I do not suggest that expectant mothers switch to a high-fat diet, based exclusively on these results, it might be interesting to take a look clinically at the effect of a mother's diet on the developing fetus," says Philip Beachy, Ph.D., an associate professor of molecular biology and genetics and a Howard Hughes Medical Institute investigator. "I'd be very interested in the effects of cholesterol levels and the presence of substances that affect cholesterol formation."

He cautions that many of the patterning events directed by these proteins take place before most women know they're pregnant.

Hedgehog and other similar proteins act like construction supervisors, helping to direct an organism's growth from a single fertilized egg into a collection of millions of structured, specialized cells. In animal experiments, hedgehog signals can turn on and off genes in many individual cells, coding for special traits needed to help create limbs, eyes, spinal column, or other structures.

In recent years, Hopkins scientists have discovered that hedgehog proteins split in two to activate. During the split, the activated form of the protein, known as the signal, becomes anchored to

Contact: Michael Purdy
Johns Hopkins Medical Institutions

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