Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking

Voelzmann, Andre; Okenve-Ramos, Pilar; Qu, Yue; Chojnowska-Monga, Monika; del Caño-Espinel, Manuela; Prokop, Andreas; Sanchez-Soriano, Natalia

Abstract

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.

Citation

Voelzmann, A., Okenve-Ramos, P., Qu, Y., Chojnowska-Monga, M., del Caño-Espinel, M., Prokop, A., & Sanchez-Soriano, N. (2016). Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking. eLife, 5, Article e14694. https://doi.org/10.7554/elife.14694

• Journal Article Type: Article
• Acceptance Date: Jul 12, 2016
• Online Publication Date: Aug 8, 2016
• Publication Date: 2016
• Deposit Date: Feb 8, 2024
• Publicly Available Date: Feb 22, 2024
• Journal: eLife
• Publisher: eLife Sciences Publications
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Article Number: e14694
• DOI: https://doi.org/10.7554/elife.14694
• Keywords: General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology; General Medicine; General Neuroscience
• Public URL: https://hull-repository.worktribe.com/output/4371713