Researchers at the University of Pennsylvania School of Medicine discovered that a key receptor protein is a critical component of the internal molecular clock in mammals. Whats more, this molecule –called Rev-erb– is sensitive to lithium and may help shed light on circadian rhythm disorders, including bipolar disorder. The findings, which also provide insight into clock-controlled aspects of metabolism, are reported in this weeks issue of Science.
"Were interested in the internal control of metabolism because feeding behavior is on a daily cycle, and hormonal activities that regulate this are circadian," says senior author Mitch Lazar, MD, PhD, Director of the Institute for Diabetes, Obesity, and Metabolism at Penn. "Many studies, including those here at Penn, suggest a relationship between the human circadian clock and metabolism. Proteins are the gears of the clock, and not much is known about what regulates protein levels within the cell."
Rev-erb was known to be a key component of the clock that exists in most cells of the body. Rev-erb inhibits clock genes called bmal and clock, but within a normal 24-hour circadian cycle the Rev-erb protein is destroyed within the cell, allowing bmal and other clock proteins to increase. Among other actions, these clock genes cause Rev-erb to increase, which again inhibits bmal and clock. "The time it takes for that to happen determines the length of the cycle–roughly 24 hours–and keeps the clock going," explains Lazar.
Karen Kreeger | EurekAlert!
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