RT info:eu-repo/semantics/article
T1 Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking
A1 Voelzmann, Andre
A1 Okenve-Ramos, Pilar
A1 Qu, Yue
A1 Chojnowska-Monga, Monika
A1 Caño Espinel, Manuela del
A1 Prokop, Andreas
A1 Sánchez Soriano, Natalia
K1 Biología
K1 Biology
K1 Neurología
K1 Neurology
K1 Medicina
K1 Medicine
AB The 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.
PB eLife Sciences Publications
YR 2016
FD 2016
LK http://hdl.handle.net/10259/8206
UL http://hdl.handle.net/10259/8206
LA eng
NO This 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.
DS Repositorio Institucional de la Universidad de Burgos
RD 10-may-2024