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dc.contributor.authorVoelzmann, Andre
dc.contributor.authorOkenve-Ramos, Pilar
dc.contributor.authorQu, Yue
dc.contributor.authorChojnowska-Monga, Monika
dc.contributor.authorCaño Espinel, Manuela del
dc.contributor.authorProkop, Andreas
dc.contributor.authorSánchez Soriano, Natalia
dc.date.accessioned2023-12-14T15:22:33Z
dc.date.available2023-12-14T15:22:33Z
dc.date.issued2016
dc.identifier.urihttp://hdl.handle.net/10259/8206
dc.description.abstractThe mechanisms regulating synapse numbers during development and ageing are essential for normal brain function and closely linked to brain disorders including dementias. Using Drosophila, we demonstrate roles of the microtubule-associated protein Tau in regulating synapse numbers, thus unravelling an important cellular requirement of normal Tau. In this context, we find that Tau displays a strong functional overlap with microtubule-binding spectraplakins, establishing new links between two different neurodegenerative factors. Tau and the spectraplakin Short Stop act upstream of a three-step regulatory cascade ensuring adequate delivery of synaptic proteins. This cascade involves microtubule stability as the initial trigger, JNK signalling as the central mediator, and kinesin-3 mediated axonal transport as the key effector. This cascade acts during development (synapse formation) and ageing (synapse maintenance) alike. Therefore, our findings suggest novel explanations for intellectual disability in Tau deficient individuals, as well as early synapse loss in dementias including Alzheimer’s disease.en
dc.description.sponsorshipThis work was made possible through funding by the BBSRC (BB/M007456/1) to NSS, by the BBSRC (BB/I002448/1) and Wellcome Trust ISSF (105610/Z/14/Z) to AP, and the German Science Foundation (DFG; VO 2071/1-1) to AV. The Bioimaging Facility microscopes used in this study were purchased with grants from the BBSRC, The Wellcome Trust and the University of Manchester Strategic Fund, and the Manchester Fly Facility where flies were kept and genetic crosses performed has been supported by funds from The University of Manchester and the Wellcome Trust (087742/Z/08/Z). We thank Meredith Lees and Egor Zindy for experimental help, Bassem Hassan, Roland Brandt and Nigel Hooper for helpful comments on the manuscript, Thomas Schwarz, Sean Sweeney, Bassem Hassan, Nick Lowe and Talila Volk for kindly providing reagents. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study.en
dc.format.mimetypeapplication/pdf
dc.language.isoenges
dc.publishereLife Sciences Publicationses
dc.relation.ispartofeLife. 2016, V. 5, e14694es
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.otherBiologíaes
dc.subject.otherBiologyen
dc.subject.otherNeurologíaes
dc.subject.otherNeurologyen
dc.subject.otherMedicinaes
dc.subject.otherMedicineen
dc.titleTau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal traffickingen
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.relation.publisherversionhttp://dx.doi.org/10.7554/eLife.14694es
dc.identifier.doi10.7554/eLife.14694
dc.identifier.essn2050-084X
dc.journal.titleeLifees
dc.volume.number5es
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones


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