Hopkins 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-I outside the cell nucleus led us to suspect that this protein must be doing more than regulate gene expression,” says Desiderio.

Under normal conditions, calcium does not flow freely into and out of cells until a demand for it – such as a muscle contraction or nerve function — triggers cells to take up the free floating element from their surroundings. Cells store calcium until still other signals occur to release it again.

“The finding was stunning to us because calcium is one of the most important messengers in cells,” says Desiderio, “and both it and TFII-I are in every cell. That affirmed our suspicion that TFII-I could be doing something important with calcium signaling.”

In one experiment, the Hopkins team knocked down the amount of TFII-I in lab-grown cells and looked for changes in calcium flow under a high-power microscope using a dye that glows when it comes in contact with calcium. A camera attached to the microscope recorded the brightness of the glow and fed that measure into a computer that calculates the amount of calcium.

Knocking down TFII-I and separately assaulting the cells with chemicals caused the cells to take up more calcium than usual.

The researchers realized that when they depleted the cells of TFII-I, the cell responded by installing more calcium channels in their surfaces that allow calcium and only calcium to enter the cell. “We think TFII-I must control calcium entry into the cell by somehow limiting the number of calcium channels at the cell's surface,” says Desiderio.

“There's good evidence suggesting that the frequency and intensity of this ebb and flow of calcium can determine a cell's response to external cues,” says Desiderio. “TFII-I may be a universal player in communication between cells, in the brain, the immune system and elsewhere.”

Media Contact

Audrey Huang EurekAlert!

More Information:

http://www.jhmi.edu

All latest news from the category: Life Sciences and Chemistry

Articles and reports from the Life Sciences and chemistry area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Back to home

Comments (0)

Write a comment

Newest articles

Lighting up the future

New multidisciplinary research from the University of St Andrews could lead to more efficient televisions, computer screens and lighting. Researchers at the Organic Semiconductor Centre in the School of Physics and…

Researchers crack sugarcane’s complex genetic code

Sweet success: Scientists created a highly accurate reference genome for one of the most important modern crops and found a rare example of how genes confer disease resistance in plants….

Evolution of the most powerful ocean current on Earth

The Antarctic Circumpolar Current plays an important part in global overturning circulation, the exchange of heat and CO2 between the ocean and atmosphere, and the stability of Antarctica’s ice sheets….

Partners & Sponsors