Functional coupling between synaptic vesicle exocytosis and recycling in mammalian synapses
Final Report Abstract
For our brain to function properly, its individual neurons need to be able to efficiently communicate with each other. While long-distance transmission of information in the brain relies on electrical signals, the gap between two neurons has to be bridged by chemical signals. This occurs at dedicated contact points, the synapses, and involves the release of neurotransmitters from synaptic vesicles. The released neurotransmitters bind to neurotransmitter receptors present on the postsynaptic neuron and thereby induce a signal cascade that triggers again an electrical signal. For this communication system to work, the presynaptic neuron needs to constantly replenish its supply of fusion-competent synaptic vesicles. Importantly, synaptic vesicle exocytosis needs to be balanced by internalization of an equal amount of membrane by endocytosis to maintain membrane homeostasis over extended periods of time and to prevent synaptic dysfunction. How synapses “know” how many vesicles have fused to match such fusion by endocytosis of an equal amount of membrane is largely unknown. The central goal of the project has been to uncover the mechanisms and the molecular machinery that enables the close coupling between the exocytosis and endocytosis of synaptic vesicle membranes. Using genetic and microscopy-based approaches, we discovered that Synaptotagmin 1, a calcium sensing protein found in synaptic vesicles, once exocytosed to the neuronal surface serves as a trigger for endocytosis of synaptic vesicle membranes. This mechanism is important as knockout mice lacking Synaptotagmin 1 die immediately after birth due to defects in neurotransmission. Moreover, we have found evidence that additional factors such as the actin cytoskeleton and special proteins that can sense the addition of membrane by measuring a parameter called tension also contribute to the process of endocytosis at mammalian synapses. Collectively, these works have advanced our understanding of neurotransmission and brain function.
Publications
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SynActJ: Easy-to-Use Automated Analysis of Synaptic Activity. Frontiers in Computer Science, 3.
Schmied, Christopher; Soykan, Tolga; Bolz, Svenja; Haucke, Volker & Lehmann, Martin
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Synaptotagmin 1-triggered lipid signaling facilitates coupling of exo- and endocytosis. Neuron, 111(23), 3765-3774.e7.
Bolz, Svenja; Kaempf, Natalie; Puchkov, Dmytro; Krauss, Michael; Russo, Giulia; Soykan, Tolga; Schmied, Christopher; Lehmann, Martin; Müller, Rainer; Schultz, Carsten; Perrais, David; Maritzen, Tanja & Haucke, Volker
