2026-10-31T15:14:12Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/82062023-12-15T01:05:25Zcom_10259_7130com_10259_5086com_10259_2604col_10259_7131

00925njm 22002777a 4500 dc Voelzmann, Andre author Okenve-Ramos, Pilar author Qu, Yue author Chojnowska-Monga, Monika author Caño Espinel, Manuela del author Prokop, Andreas author Sánchez Soriano, Natalia author 2016 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. http://hdl.handle.net/10259/8206 10.7554/eLife.14694 2050-084X Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking