Researchers from the Max Planck Institute for Biophysical Chemistry (Goettingen, Germany) have recently published an article in JBC that proofs a very strong cooperativity between the binding of phospholipid PIP2 and calcium to synaptotagmin-1.Upon arrival of an action potential in the synapse, ion channels open resulting in an increase in cytoplasmic calcium. This increase in calcium concentration is sensed by synaptotagmin-1 which mediates exocytosis of synaptic vesicles and release of neurotransmitter in the synaptic cleft. The precise mechanism of action of synaptotagmin-1 is unknown but involves both binding to calcium and to the phospholipid PIP2 in the plasma membrane.
“In this study, we used MST to precisely quantify the cooperativity of PIP2 and calcium binding. PIP2-binding to synaptotagmin-1 resulted in a 40-fold higher affinity for calcium, and this result is of fundamental importance for our understanding of neuronal exocytosis. Given (i) the relatively high affinity of synaptotagmin-1 for both PIP2 and calcium, (ii) the low solubility of PIP2 and (iii) that synaptotagmin-1 is prone to aggregate at high protein concentrations, we cannot think of any technique other than MST that would allow studying this cooperative binding to such detail. Moreover, due to the very high sensitivity of MST, we estimate that the same amount of synaptotagmin-1 suffices to record about 10,000 times more calcium binding curves with MST compared to NMR or ITC”, says Dr. Geert van den Bogaart from the Department of Neurobiology. NanoTemper congratulates the authors for the publication of this important study.
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