Featured Research

from universities, journals, and other organizations

Regulation process of protein linked to bipolar disorder, researchers find

Date:
June 11, 2014
Source:
Tufts University
Summary:
New insight into a protein associated with bipolar disorder has been gained by recent research. The study 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. 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 team also discovered that signaling by these calcium channels is most active in the so-called "off" or "resting" phase.

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.

Related Articles


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.

Store-operated calcium channels (SOCC) are a type of calcium channel found in all cells. These channels are activated when stores of calcium inside the cell are reduced. A calcium sensor called stromal interaction molecule 1 (STIM1) is responsible for calcium entry into the cell through SOCCs.

To determine whether STIM1 controlled Sp4 breakdown, the researchers reduced STIM1 levels in cells and measured Sp4 levels. A control group of cells contained normal levels of STIM1, while a comparison group contained reduced STIM1 levels. Both cell groups were placed in a solution for 60 minutes to place them into their "resting" state.

The cells in the control group displayed significantly less Sp4 when at rest while, in contrast, cells in the comparison group -- those with reduced STIM1 levels -- had higher Sp4 levels.

"These findings provide evidence that STIM1 is required for the breakdown of Sp4 when the cell hyperpolarizes, which tell us the presence of STIM1 directly influences Sp4 levels in neurons," said first author, Jasmin Lalonde, Ph.D., a former postdoctoral fellow in Gill's lab and now a research fellow at the Center for Human Genetic Research and the department of neurology at the Massachusetts General Hospital.

This is ongoing work by Gill to understand the role of Sp4 in bipolar disorder. Some of Gill's previous research, performed in collaboration with researchers from Spain, found that Sp4 levels were lower in two areas of the brain in postmortem samples from patients with bipolar disorder. In a study published in May of this year in the Journal of Neurochemistry, she and her team determined that one mechanism of Sp4 regulation is a glutamate receptor called the NMDA receptor.


Story Source:

The above story is based on materials provided by Tufts University. The original article was written by Siobhan Gallagher. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. Lalonde, G. Saia, G. Gill. Store-Operated Calcium Entry Promotes the Degradation of the Transcription Factor Sp4 in Resting Neurons. Science Signaling, 2014; 7 (328): ra51 DOI: 10.1126/scisignal.2005242

Cite This Page:

Tufts University. "Regulation process of protein linked to bipolar disorder, researchers find." ScienceDaily. ScienceDaily, 11 June 2014. <www.sciencedaily.com/releases/2014/06/140611093048.htm>.
Tufts University. (2014, June 11). Regulation process of protein linked to bipolar disorder, researchers find. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/2014/06/140611093048.htm
Tufts University. "Regulation process of protein linked to bipolar disorder, researchers find." ScienceDaily. www.sciencedaily.com/releases/2014/06/140611093048.htm (accessed October 31, 2014).

Share This



More Health & Medicine News

Friday, October 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

U.S. Ebola Response Measures Demonstrated

U.S. Ebola Response Measures Demonstrated

AP (Oct. 31, 2014) Officials in the Washington area showed off Ebola response measures being taken at Dulles International Airport and the National Institutes of Health. (Oct. 31) Video provided by AP
Powered by NewsLook.com
Fauci Says Ebola Risk in US "essentially Zero"

Fauci Says Ebola Risk in US "essentially Zero"

AP (Oct. 30, 2014) NIAID Director Anthony Fauci said the risk of Ebola becoming an epidemic in the U.S. is essentially zero Thursday at the Washington Ideas Forum. He also said an Ebola vaccine will be tested in West Africa in the next few months. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Nurse Defies Ebola Quarantine With Bike Ride

Nurse Defies Ebola Quarantine With Bike Ride

AP (Oct. 30, 2014) A nurse who vowed to defy Maine's voluntary quarantine for health care workers who treated Ebola patients followed through on her promise Thursday, leaving her home for an hour-long bike ride. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Pot-Infused Edibles Raise Concerns in Colorado

Pot-Infused Edibles Raise Concerns in Colorado

AFP (Oct. 30, 2014) Colorado may have legalized marijuana for recreational use, but the debate around the decision still continues, with a recent - failed - attempt to ban cannabis-infused edibles. Duration: 01:53 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins