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Content archived on 2024-05-29

Maintaining neurotransmission: clathrin-mediated endocytosis and kiss-and-run

Objective

Our brain consists of over a 100 billion neurons, organized into neuronal circuits transmitting electrical pulses. Hence, the integrity of a circuit depends on reliable neuronal communication: if a neuron fails, the circuit fails. The importance to maintain neuronal communication is underscored by numerous psychiatric disorders, such as schizophrenia, epilepsy and drug addiction arising from defects in specific circuits. Neurons in these circuits communicate by releasing neurotransmitters from synaptic vesicles and to maintain communication neurons dependent on efficient recycling of synaptic vesicle pools. The work focuses on understanding mechanisms of vesicle recycling using morphological and functional assays. The studies indicate the existence of 2 recycling pathways: clathrin-mediated endocytosis (CME), where membranes invaginate to form vesicles, and kiss-and-run, where vesicles form a transient fusion pore and recycle locally. While many components of CME are identified and shown to interact biochemically, few are analysed in vivo.

CME will be studied using functional analyses of newly identified genes as well as by using novel imaging strategies involving FRET, allowing to visualize protein interactions while vesicles form in real-time, revealing nov el types of synaptic plasticity. The existence of alternative vesicle recycling modes, like kiss-and-run, remains controversial, because no specific protein required for it has been identified. The group found that when CME is blocked in endophilin and synaptojan in mutants some transmission akin to kiss-and-run persists.

Based on this a genetic strategy to isolate the first molecular components of kiss-and-run, paving the way towards better understanding of the process is outlined. Taken together, the work seeks to elucidate mechanisms of vesicle retrieval. By understanding processes underlying neuro-communication better, valuable insight into the basis of normal and pathological brain function will be obtained.

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Keywords

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Topic(s)

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Call for proposal

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FP6-2005-MOBILITY-8
See other projects for this call

Funding Scheme

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EXT - Marie Curie actions-Grants for Excellent Teams

Coordinator

FLANDERS INTERUNIVERSITY INSTITUTE FOR BIOTECHNOLOGY VZW
EU contribution
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Total cost

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