Navigation Links
Johns Hopkins scientists identify a key to body's use of free calcium
Date:1/23/2014

Scientists at Johns Hopkins report they have figured out a key step in how "free" calcium the kind not contained in bones is managed in the body, a finding that could aid in the development of new treatments for a variety of neurological disorders that include Parkinson's disease.

Appearing online this week in Nature Chemical Biology, the researchers describe their use of tiny "lights" and chemical "leashes" to unveil how calcium is controlled.

Electrical signals carried by free-floating calcium ions are "wildly important to keeping the second-by-second functions of the body going," says David Yue, M.D., Ph.D., professor of biomedical engineering and neuroscience at The Johns Hopkins University.

Yue, who led the research team of graduate students Philemon Yang and Manu Ben Johny, explains that large proteins called calcium channels are the gatekeepers that determine when calcium enters cells. Embedded in cell membranes, these channels open and shut to regulate calcium flow into the cell. When calcium goes into cells, it sets off a cascade of vital activity, but just the right amount of calcium must enter otherwise, problems arise.

To achieve this balance, two chemical regulators bind to calcium channels as a brake and accelerator for calcium entry. Calmodulin, one type of calcium channel-binding protein, stops calcium from flowing through, while other proteins, known as calcium- Yue, who led the research team of graduate students Philemon Yang and Manu Ben Johny, explains that large proteins called calcium channels are the gatekeepers that determine when calcium enters cells.

Embedded in cell membranes, these channels open and shut to regulate calcium flow into the cell. When calcium goes into cells, it sets off a cascade of vital activity, but just the right amount of calcium must enter otherwise, problems arise. To achieve this balance, two chemical regulators bind to calcium channels as a brake and accelerator for calcium entry. Calmodulin, one type of calcium channel-binding protein, stops calcium from flowing through, while other proteins, known as calcium-binding proteins, accelerate calcium entry.

In their research, Yue and his colleagues examined specific calcium channels embedded in the membranes of nerve cells in the brain to see how calmodulin and CaBP4, a particular calcium-binding protein, latch onto the channels.

They rigged the odds in favor of calmodulin binding by genetically engineering calcium channels that were tethered to calmodulin by a short, flexible strand of amino acids. But to their surprise, Yue says, calcium-binding proteins stuck to the calcium channels at the same time, suggesting that each regulator has its own parking space on the channel, whereas previous theories suggested a single space.

To further examine the relationships among these regulators of calcium, the scientists used markers that glow in different colors and attached them to calcium channels, calmodulin and CaBP4. When two molecules locked together, the color changed. By measuring color changes, the researchers could then tell which molecules bound to each other.

In their research, Yue and his colleagues examined specific calcium channels embedded in the membranes of nerve cells in the brain to see how calmodulin and CaBP4, a particular calcium-binding protein, latch onto the channels.

They rigged the odds in favor of calmodulin binding by genetically engineering calcium channels that were tethered to calmodulin by a short, flexible strand of amino acids. But to their surprise, Yue says, calcium-binding proteins stuck to the calcium channels at the same time, suggesting that each regulator has its own parking space on the channel, whereas previous theories suggested a single space.

To further examine the relationships among these regulators of calcium, the scientists used markers that glow in different colors and attached them to calcium channels, calmodulin and CaBP4. When two molecules locked together, the color changed. By measuring color changes, the researchers could then tell which molecules bound to each other.

"Our experiments established that calmodulin and calcium-binding proteins work by binding to distinct parts of the calcium channel," Yue says. "More generally, we have been able to investigate how large molecules such as these function in living cells."

The "live light show" permitted by the use of light markers should help scientists develop new drugs that target calcium channels, Yue adds. Some such drugs already exist, including calcium channel blockers that lower blood pressure by targeting a particular kind of calcium channel found in blood vessels.

Blocking calcium channels might help with other diseases, too, Yue says. For example, researchers have found that an overload of calcium in certain parts of the brain may drive some neurodegenerative diseases, such as Parkinson's. Blocking the calcium channels found in those trouble spots the kind of calcium channels in Yue's study could be a way to fight the debilitating brain disease.


'/>"/>

Contact: Catherine Kolf
ckolf@jhmi.org
443-287-2251
Johns Hopkins Medicine
Source:Eurekalert

Related biology news :

1. Johns Hopkins researchers uncover genes at fault for cystic fibrosis-related intestinal obstruction
2. Johns Hopkins researchers link 2 biological risk factors for schizophrenia
3. The Johns Hopkins Center for Inherited Disease Research receives $101 million
4. 3 Johns Hopkins researchers named AAAS Fellows
5. NREL and Johnson Matthey announce 5-year collaboration on biofuels
6. 3 Johns Hopkins researchers recognized for medical inventions
7. Johns Hopkins And Belgian research center to expand health care applications for silicon nanotech
8. 4 Johns Hopkins researchers named AAAS Fellows
9. Genetic predictors of postpartum depression uncovered by Hopkins researchers
10. Stanford scientists develop gene therapy approach to grow blood vessels in ischemic limbs
11. Queens scientists seek vaccine for Pseudomonas infection
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/13/2017)... N.Y. , Jan. 13, 2017 ... technology solutions for the homecare industry, including Electronic ... homecare industry expert, Justin Jugs, as Senior Vice ... more than 15 years of homecare experience to ... in developing strategic plans to align Sandata,s suite ...
(Date:1/12/2017)... PORTLAND, Oregon and PUNE, India , January 12, 2017 ... Technology Market: Opportunities and Forecasts, 2015 - 2022," projects that the global biometric technology ... CAGR of 19.4% from 2016 to 2022. Continue Reading ... ... ...
(Date:1/6/2017)... Jan. 6, 2017  Privately-held CalciMedica, Inc., announced ... healthy volunteers of a novel calcium release-activated calcium ... pancreatitis. Acute pancreatitis, sudden painful ... disorder, but can be very serious.  In severe cases ... where extended hospital stays, time in the ICU ...
Breaking Biology News(10 mins):
(Date:1/18/2017)... PA (PRWEB) , ... January 18, 2017 , ... ... operations again at the CHI SCOPE Summit for Clinical Ops Executives (Hyatt Regency ... engaging panel discussions to examine vital clinical research issues such as trial performance ...
(Date:1/18/2017)... ... ... Thirty-six startup companies in University City and Center City have been awarded ... Development in 2016 as part of the Keystone Innovation Zone (KIZ) Tax Credit Program. ... represent the highest number of awards to the largest number of companies in the ...
(Date:1/18/2017)... Jan. 18, 2017  Caris Life Sciences, a ... Foundation, the largest private funder of pancreatic cancer ... evaluating the impact of immunotherapy in the treatment ... enrollment services to identify potential trial candidates based ... treating physicians and study investigators. The Lustgarten Foundation ...
(Date:1/17/2017)... ... January 17, 2017 , ... LGC Maine ... its VALIDATE® SP2 calibration verification / linearity test kit. VALIDATE® SP2 evaluates Albumin, ... VALIDATE® SP2 kit is prepared using the CLSI recommended “equal delta” method for ...
Breaking Biology Technology: