A research team from the RIKEN Brain Science Institute in Wako has visualized and accurately modeled the molecular changes that open and close the internal membrane channels for calcium ions within cells1. The ions moving through these channels act as intracellular messengers, relaying information that regulates the activity of the proteins that control many critical processes of life and death—from fertilization through to development, metabolism and, ultimately, death.
Figure 1: A cell emitting fluorescent signals as a result of attaching specialized proteins to two of its channel-forming IP3Rs (scale bar, 10 µm). Copyright : PNAS
Previous work by the team showed that inositol trisphosphate (IP3) and calcium ions are involved in regulating channel opening and closing. The channels are formed from complexes of four IP3 receptors (IP3R) that bind IP3 and calcium. At low concentrations of calcium ions, channel opening is stimulated; but at higher levels, it is inhibited. Although cell biologists have proposed models depicting this process, they had failed to collect any definitive evidence supporting a particular the mechanism, until now.
In live cells, Takayuki Michikawa, Katsuhiko Mikoshiba and their colleagues attached fluorescent proteins to two of the channel-forming IP3Rs because these receptors change shape in response to the binding of IP3 and calcium, and energy flows between this pair of proteins in a process known as Förster resonance energy transfer (FRET) (Fig. 1). In a detectable way, FRET changes the fluorescent light emitted, so the impact of such links on the conformation of the channel can be studied.
The researchers found there were at least five binding sites on each IP3R, one for IP3 and at least four for calcium. Binding IP3 tended to bring the receptors forming the channel closer together, while calcium tended to make them relax. But the effects of combining the two were not simply additive. At a constant level of IP3, they observed an optimum concentration of calcium that had the most impact on opening the channel.
From these results, the researchers proposed a model whereby IP3 and calcium ions compete with one another—the binding of IP3 prevents calcium linking to certain sites, and vice versa. High concentrations of calcium prevent IP3 from binding at all. Further, the researchers proposed two different types of calcium binding sites: low-affinity sites responsible for channel activation, and high-affinity sites for inactivation.“During the past five years, we have succeeded in visualizing IP3 dynamics and calcium pump activity,” Michikawa and Mikoshiba say. “In combination with the model for the calcium release channel described in this study, we are now ready to understand what happens in living cells during calcium ion oscillations.”
First SARS-CoV-2 genomes in Austria openly available
03.04.2020 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
Do urban fish exhibit impaired sleep? Light pollution suppresses melatonin production in European perch
03.04.2020 | Leibniz-Institut für Gewässerökologie und Binnenfischerei (IGB)
Drops of water falling on or sliding over surfaces may leave behind traces of electrical charge, causing the drops to charge themselves. Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz have now begun a detailed investigation into this phenomenon that accompanies us in every-day life. They developed a method to quantify the charge generation and additionally created a theoretical model to aid understanding. According to the scientists, the observed effect could be a source of generated power and an important building block for understanding frictional electricity.
Water drops sliding over non-conducting surfaces can be found everywhere in our lives: From the dripping of a coffee machine, to a rinse in the shower, to an...
90 million-year-old forest soil provides unexpected evidence for exceptionally warm climate near the South Pole in the Cretaceous
An international team of researchers led by geoscientists from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) have now...
The bacteria that cause tuberculosis need iron to survive. Researchers at the University of Zurich have now solved the first detailed structure of the transport protein responsible for the iron supply. When the iron transport into the bacteria is inhibited, the pathogen can no longer grow. This opens novel ways to develop targeted tuberculosis drugs.
One of the most devastating pathogens that lives inside human cells is Mycobacterium tuberculosis, the bacillus that causes tuberculosis. According to the...
An international team with the participation of Prof. Dr. Michael Kues from the Cluster of Excellence PhoenixD at Leibniz University Hannover has developed a new method for generating quantum-entangled photons in a spectral range of light that was previously inaccessible. The discovery can make the encryption of satellite-based communications much more secure in the future.
A 15-member research team from the UK, Germany and Japan has developed a new method for generating and detecting quantum-entangled photons at a wavelength of...
Together with their colleagues from the University of Würzburg, physicists from the group of Professor Alexander Szameit at the University of Rostock have devised a “funnel” for photons. Their discovery was recently published in the renowned journal Science and holds great promise for novel ultra-sensitive detectors as well as innovative applications in telecommunications and information processing.
The quantum-optical properties of light and its interaction with matter has fascinated the Rostock professor Alexander Szameit since College.
02.04.2020 | Event News
26.03.2020 | Event News
23.03.2020 | Event News
03.04.2020 | Materials Sciences
03.04.2020 | Life Sciences
03.04.2020 | Life Sciences