PUBLIC RELEASE DATE:

11-Jun-2014

Contact: Siobhan Gallagher siobhan.gallagher@tufts.edu 617-636-6586 Tufts University, Health Sciences Campus

BOSTON (June 11, 2014) Researchers from Tufts have gained new insight into a protein associated with bipolar disorder. The study, published in the June 3 issue of Science Signaling, reveals that calcium channels in resting neurons activate the breakdown of Sp4, which belongs to a class of proteins called transcription factors that regulate gene expression.

This study, led by Grace Gill, identifies a molecular mechanism regulating Sp4 activity. Her previous research had determined that reduced levels of Sp4 in the brain are associated with bipolar disorder. Her work overall suggests that misregulation of Sp4 may contribute to the development of bipolar disorder.

"Understanding how transcription factors like Sp4 are regulated may provide us with ways to change neuronal gene expression to treat symptoms of mental illness, including bipolar disorder," said Gill, Ph.D., an associate professor in the department of developmental, molecular & chemical biology at Tufts University School of Medicine and member of the neuroscience; genetics; and cell, molecular and developmental biology program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.

The main goal of the study was to determine whether a specific type of calcium channel store-operated calcium channels drive the breakdown of Sp4 protein. Along the way, however, the research team also discovered that signaling by these calcium channels is most active in the so-called "off" or "resting" phase.

"The calcium-signaling regulation of Sp4 during the resting phase was unexpected and suggests two things: resting neurons are more active than we had thought and calcium signaling influences gene expression in both active and resting neurons," Gill said.

"We tend to think about cells being "on" or "off," but the reality of the biology is far more complex. Cells are always busy," she continued.

In neurons cells that can be stimulated by electrical signals transcription factors are regulated by calcium entry that is initiated when the cell depolarizes. Depolarization occurs when the overall voltage of the cell is increased. This is the "on" or "active" state for the cell. In contrast, when the cell's voltage is decreased, hyperpolarization occurs. This is called the "off" or "resting" phase for the cell.

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Researchers identify regulation process of protein linked to bipolar disorder

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