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Researchers Uncover Critical Player in Cell Communication

Johns Hopkins researchers have teased out the function of a protein implicated in Williams-Beuren syndrome, a rare cognitive disorder associated with overly social behavior// and lack of spatial awareness. Called TFII-I, or TF “two eye,” the protein long known to help control a cell’s genes also controls how much calcium a cell takes in, a function critical for all cells, including nerves in the brain. The study will be published this week in Science.

“While the previously described function of TFII-I very well also could contribute to the cognitive defects of Williams-Beuren syndrome, its role controlling calcium makes much more sense,” says Stephen Desiderio, M.D., Ph.D., a professor of molecular biology and genetics and director of the Institute of Basic Biomedical Sciences at Hopkins. And, says Desiderio, others have shown that defects in a cell’s ability to take in calcium can lead to other neurological and behavioral conditions.

Williams-Beuren syndrome is associated with craniofacial defects, problems with the aorta and a very specific mental retardation that causes those affected to be talkative, sociable and empathetic but at the same time have significant spatial learning defects. Those affected are highly expressive, have exceptionally strong language abilities and “can talk up a storm,” for example. But at the same time, they are poor at global organization, having problems re-creating patterns in drawings. The syndrome occurs in roughly one in 25,000 births and is caused by a deletion of a small section of chromosome 7 that contains several genes, including the gene that encodes the TFII-I protein.

The discovery came after Desiderio and his team used biochemical “bait” to fish for candidate proteins that physically bind to TFII-I. The fishing expedition returned one protein known to control when and how much calcium a cell takes in.

“The partner we found in the fishing experiment and the abundance of TFII-
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