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Elevated synaptic vesicle release probability in synaptophysin/gyrin family quadruple knockouts.

Raja MK, Preobraschenski J, Del Olmo-Cabrera S, Martinez-Turrillas R, Jahn R, Perez-Otano I, Wesseling JF.

elife. pii: e40744
Published: 2019 May 15

Synaptophysins and synaptogyrins are a widely-expressed family of synaptic vesicle membrane proteins, possibly present in every synapse throughout the animal kingdom. The function has been a mystery until now. Other extensively studied synaptic vesicle proteins play important roles in catalyzing exocytosis, and deletion prevents neurotransmitter from being released into the extracellular space. Here we show that deleting synaptophysin/gyrin family members has the opposite effect. Catalysis of exocytosis becomes more efficient, not less. The results indicate that family members normally function as negative regulators of neurotransmission. Neuroscientists have long known that catalysis of exocytosis is inefficient at many types of synapses, but assumed this was because the machinery is built out of low-tolerance biological materials that cannot do better. The presence of negative regulators in possibly every synapse indicates that the inefficiency is built in by design - a feature, not a bug of normal synaptic function - which changes how we think about how neural circuits go about processing information.

From left to right: Sergio Del olmo Cabrera, John F. Wesseling, Isabel Pérez Otaño

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