Cells rely on calcium as a universal means of communication. For example, a sudden rush of calcium can trigger nerve cells to convey thoughts in the brain or cause a heart cell to beat.
A longstanding mystery has been how cells and molecules manage to appropriately sense and respond to the variety of calcium fluctuations within cells.
Reporting in the June 27 issue of Cell, a team of biomedical engineers at the Johns Hopkins School of Medicine has discovered how the calcium sensor protein calmodulin can gauge both the local flow of calcium, in through the closest channel, as well as the global calcium flow entering the many channels across the entire cell.
“It’s like being at a cocktail party where the easiest person to listen to is the one closest to you, but we all have the ability to keep an ear out for other interesting conversations going on throughout the room,” says David Yue, M.D., Ph.D., a professor of biomedical engineering at Hopkins. “It turns out that calmodulin is doing a similar thing, sensing the calcium coming through the closest channel through one ear while the other ear ‘listens’ to the calcium coming through distant channels across the cell.”
Normally, calmodulin is positioned right near each calcium channel. Several years ago, scientists discovered that calmodulin somehow can switch its sensory focus between local calcium and global calcium entering the cell through channels at a distance.
The calmodulin protein, explains Yue, is made of two ball-like lobes, and it’s these two lobes that act as the different calcium-sensing “ears.” The C lobe listens locally and the N lobe listens globally, across the whole cell. To figure out how calmodulin’s two lobes can sense different sources of calcium, the team took a two-pronged approach.
First, they used computers to perform mathematical simulations that tested different potential calcium detection mechanisms of the calmodulin lobes. Others have shown that the C lobe of calmodulin hangs onto calcium for a long time, whereas the N lobe lets go rapidly. Their simulations suggested that these slight differences in calcium holding time might play a role in calmodulin’s ability to sense both local and global calcium levels. “Once a local calcium ion sticks to the C lobe, it seldom lets go, and so the local calcium dominates,” says Yue.
By contrast, the N lobe would rapidly let go of calcium and then be empty and available to bind calcium entering the cell from distant calcium channels, allowing reception of global calcium. Similar to the cocktail party, it’s easiest to catch other conversations during the pauses in your own conversation.
The research team then verified their mathematical predictions by testing real calmodulin proteins attached to calcium channels. Using a new approach, they precisely controlled calcium pulses through single calcium channels and watched how calmodulin responded. They were able to confirm the mathematical models.
Understanding the language of calcium is critical for understanding how cells communicate, says Yue, and also important for understanding neural diseases. For instance, early antipsychotic drugs may work by blocking calmodulin action. “Now that we are learning how these drugs actually work,” Yue says, “we can contribute our new understanding of calmodulin to the design of next-generation drugs with greater potency and fewer side effects.”
The research was funded by the National Institutes of Health.
Authors on the paper are Michael Tadross, Ivy Dick and Yue, all of Hopkins.
Audrey Huang | Newswise Science News
Brought to light – chromobodies reveal changes in endogenous protein concentration in living cells
21.09.2018 | NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen
A one-way street for salt
21.09.2018 | Julius-Maximilians-Universität Würzburg
The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.
This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.
Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...
Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.
"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...
A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.
Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...
Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.
An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...
21.09.2018 | Event News
03.09.2018 | Event News
27.08.2018 | Event News
21.09.2018 | Physics and Astronomy
21.09.2018 | Life Sciences
21.09.2018 | Event News