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Overview Nerve cells in the brain have a highly spatially diverse cellular and subcellular architecture including axon, cell body, and dendrites as major cellular compartments, in addition to subcellular membrane microdomains such as spines, synapses and the secretory and endosomal networks. To ensure efficient signaling between neurons, and to ensure that the correct levels of neuronal network activity are maintained, it is critical that mechanisms exist to tightly regulate the selective transport and localisation of ion channels, receptors and organelles to specific neuronal locations. We are interested in understanding the contribution played by intracellular transport and membrane trafficking of channels, transporters and organelles in regulating the formation, activity and plasticity of synapses. We focus on three major research themes: Firstly, we are studying the molecular and cellular mechanisms regulating the function and membrane trafficking of neurotransmitter receptors (with a particular focus on GABA-A receptors) and transporters and the role this plays in controlling synaptic transmission and the levels of neuronal excitability in the brain. We are similarly interested in how the function of synapses can be controlled by the regulated trafficking of organelles such as mitochondria. Secondly, we concentrate on how intracellular transport is regulated by post-translational modifications (such as phosphorylation, palmitoylation and ubiquitination) and signalling pathways that alter intracellular calcium levels. Thirdly, we wish to understand better how the trafficking of receptors, transporters and other cargo may be altered in neurological and neuropsychiatric diseases including Parkinson's, Alzheimer's and Huntington's diseases, autism and schizophrenia. We combine the use of various techniques, including molecular and cell biology, protein biochemistry, patch clamp electrophysiology, neuronal transfection, and fixed and live cell confocal and CCD imaging. We also use fluorescent protein and Quantum Dot labeling approaches to study the membrane dynamics, localisation and trafficking of proteins and organelles of interest.
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Christian Covill-Cooke, Brian Kwizera,Guillermo López-Doménech, Caleb OD Thompson,Ngaam J Cheung, Ema Cerezo, Martin Peterka,Josef T Kittler,Benoît Kornmann
bioRxiv (Cold Spring Harbor Laboratory)no. 4 (2024): 595-614
Current opinion in neurobiology (2023): 102747-102747
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