Calcium is an important signaling molecule in almost all cells. Blood platelets, called thrombocytes in technical terms, are activated by calcium and then contribute to hemostasis and wound closure. However, misdirected activation of the blood platelets through uncontrolled calcium signals can also lead to acutely life-threatening events such as thromboses, heart attacks and strokes, as well as triggering inflammatory reactions in the blood vessels.
So far, the molecule stromal interaction molecule 1 (STIM1) was known as an essential component in the regulation of calcium signals. However, it has this function in almost all cells in the body and a loss of STIM1 therefore has strong effects such as the weakening of the immune system. For this reason, it is not a suitable target structure for drug development.
"In our study, we were able to identify the previously unknown molecule BIN2 (bridging integrator 2) as a new interaction partner of STIM1 in blood platelets and also show that BIN2 also interacts with another component of the calcium machinery," explains the senior author. The special thing about BIN2 is that it occurs very specifically in blood platelets and not, like STIM1, in many other cells. “This allows us to target the platelets precisely without disrupting the functions in other cells,” adds doctoral student who played a key role in the study. The study was published in the Journal of Clinical Investigation.
"Using super-high-resolution fluorescence microscopy, we were able to demonstrate that the molecules STIM1 and BIN2 colocalize in the platelet at certain intervals and thus underpin the biochemical data," explains another doctoral student.
Mice that do not have BIN2 show greatly reduced calcium signals in the platelets. This results in smaller blood clots in their blood vessels after damage to the vessel wall, the animals are partially protected from arterial thrombosis and strokes have a milder course. This shows that molecules like BIN2 could be a starting point for drug development against thrombosis, heart attacks and strokes. To do this, the exact molecular mechanisms and other interaction partners must now be investigated.
A new protein controlling platelet aggregation identified
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