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During the priming step that leaves synaptic vesicles ready for neurotransmitter release, the SNARE syntaxin-1 transitions from a closed conformation that binds Munc18-1 tightly to an open conformation within the highly stable SNARE complex. Control of this conformational transition is important for brain function, but the underlying mechanism is unknown. NMR and fluorescence experiments now show that the Munc13-1 MUN domain, which plays a central role in vesicle priming, markedly accelerates the transition from the syntaxin-1-Munc18-1 complex to the SNARE complex. This activity depends on weak interactions of the MUN domain with the syntaxin-1 SNARE motif, and probably with Munc18-1. Together with available physiological data, these results provide a defined molecular basis for synaptic vesicle priming, and they illustrate how weak protein-protein interactions can play crucial biological roles by promoting transitions between high-affinity macromolecular assemblies.
Pubmed ID: 21499244 RIS Download
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NEURON is a simulation environment for modeling individual neurons and networks of neurons. It provides tools for conveniently building, managing, and using models in a way that is numerically sound and computationally efficient. It is particularly well-suited to problems that are closely linked to experimental data, especially those that involve cells with complex anatomical and biophysical properties. NEURON has benefited from judicious revision and selective enhancement, guided by feedback from the growing number of neuroscientists who have used it to incorporate empirically-based modeling into their research strategies. NEURON's computational engine employs special algorithms that achieve high efficiency by exploiting the structure of the equations that describe neuronal properties. It has functions that are tailored for conveniently controlling simulations, and presenting the results of real neurophysiological problems graphically in ways that are quickly and intuitively grasped. Instead of forcing users to reformulate their conceptual models to fit the requirements of a general purpose simulator, NEURON is designed to let them deal directly with familiar neuroscience concepts. Consequently, users can think in terms of the biophysical properties of membrane and cytoplasm, the branched architecture of neurons, and the effects of synaptic communication between cells. * helps users focus on important biological issues rather than purely computational concerns * has a convenient user interface * has a user-extendable library of biophysical mechanisms * has many enhancements for efficient network modeling * offers customizable initialization and simulation flow control * is widely used in neuroscience research by experimentalists and theoreticians * is well-documented and actively supported * is free, open source, and runs on (almost) everything
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