Coupling of Ca²+-triggered unclamping and membrane fusion during neurotransmitter release
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Resumen del artículo
Molecular dynamics simulations suggest that neurotransmitter release is accomplished by a highly cooperative machinery whose calcium-triggered unclamping and membrane-fusing functionalities are intrinsically inseparable. The model reproduces experimental dependencies, providing a unified account of calcium-triggered unclamping and SNARE-mediated membrane fusion, which occur as contemporaneous and coupled processes.
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Computer simulations of the machinery that releases neurotransmitters in the brain reveal that releasing the neurotransmitters and the fusion of membranes are coupled processes, and protein flexibility is important for proper function.
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Explicación de la calificación
This study uses sophisticated computational modeling to provide a detailed molecular mechanism of neurotransmitter release, addressing some of the limitations of previous, phenomenological models. The inclusion of protein flexibility and the dynamic SNARE complex assembly provide a more realistic representation of the process. The model reproduces several experimental observations providing insights into some controversial aspects of the field like the relation between calcium cooperativity and release, the plateau at high calcium concentrations and the determinants of release probabilities. Although the model uses simplifications and does not include all the components of the neurotransmitter release machinery, it provides a significant advance in the field with the potential to motivate future experimental work.
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