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dc.contributor.authorYates, Darran M
dc.contributor.authorManser, Catherine
dc.contributor.authorDe Vos, Kurt J
dc.contributor.authorShaw, Christopher E
dc.contributor.authorMcLoughlin, Declan M
dc.contributor.authorMiller, Christopher C J
dc.date.accessioned2011-04-27T09:31:46Z
dc.date.available2011-04-27T09:31:46Z
dc.date.issued2009-04
dc.identifier.citationNeurofilament subunit (NFL) head domain phosphorylation regulates axonal transport of neurofilaments. 2009, 88 (4):193-202 Eur. J. Cell Biol.en
dc.identifier.issn1618-1298
dc.identifier.pmid19147253
dc.identifier.doi10.1016/j.ejcb.2008.11.004
dc.identifier.urihttp://hdl.handle.net/10147/128719
dc.description.abstractNeurofilaments are the intermediate filaments of neurons and are synthesised in neuronal cell bodies and then transported through axons. Neurofilament light chain (NFL) is a principal component of neurofilaments, and phosphorylation of NFL head domain is believed to regulate the assembly of neurofilaments. However, the role that NFL phosphorylation has on transport of neurofilaments is poorly understood. To address this issue, we monitored axonal transport of phosphorylation mutants of NFL. We mutated four known phosphorylation sites in NFL head domain to either preclude phosphorylation, or mimic permanent phosphorylation. Mutation to preclude phosphorylation had no effect on transport but mutation of three sites to mimic permanent phosphorylation inhibited transport. Mutation of all four sites together to mimic permanent phosphorylation proved especially potent at inhibiting transport and also disrupted neurofilament assembly. Our results suggest that NFL head domain phosphorylation is a regulator of neurofilament axonal transport.
dc.language.isoenen
dc.relation.urldoi:10.1016/j.ejcb.2008.11.004en
dc.subject.meshAnimals
dc.subject.meshAxonal Transport
dc.subject.meshAxons
dc.subject.meshCells, Cultured
dc.subject.meshIntermediate Filaments
dc.subject.meshMutant Proteins
dc.subject.meshNeurons
dc.subject.meshPhosphorylation
dc.subject.meshRats
dc.subject.meshTransfection
dc.titleNeurofilament subunit (NFL) head domain phosphorylation regulates axonal transport of neurofilaments.en
dc.typeArticleen
dc.contributor.departmentMRC Centre for Neurodegeneration Research, Department of Neuroscience P037, Institute of Psychiatry, King's College London, De Crespigny Park, Denmark Hill, London SE58AF, UK.en
dc.identifier.journalEuropean journal of cell biologyen
dc.description.provinceLeinster
html.description.abstractNeurofilaments are the intermediate filaments of neurons and are synthesised in neuronal cell bodies and then transported through axons. Neurofilament light chain (NFL) is a principal component of neurofilaments, and phosphorylation of NFL head domain is believed to regulate the assembly of neurofilaments. However, the role that NFL phosphorylation has on transport of neurofilaments is poorly understood. To address this issue, we monitored axonal transport of phosphorylation mutants of NFL. We mutated four known phosphorylation sites in NFL head domain to either preclude phosphorylation, or mimic permanent phosphorylation. Mutation to preclude phosphorylation had no effect on transport but mutation of three sites to mimic permanent phosphorylation inhibited transport. Mutation of all four sites together to mimic permanent phosphorylation proved especially potent at inhibiting transport and also disrupted neurofilament assembly. Our results suggest that NFL head domain phosphorylation is a regulator of neurofilament axonal transport.


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