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



Voelzmann, A, Okenve-Ramos, P, Qu, Y, Chojnowska-Monga, M, del Caño-Espinel, M, Prokop, A and Sanchez-Soriano, N
(2016) Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking. eLife, 5 (AUGUST). e14694-.

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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.

Item Type: Article
Uncontrolled Keywords: Brain, Neurons, Synapses, Microtubules, Animals, Humans, Drosophila melanogaster, Dementia, Alzheimer Disease, Disease Models, Animal, Microfilament Proteins, JNK Mitogen-Activated Protein Kinases, tau Proteins, Drosophila Proteins, Signal Transduction, Cell Movement, Axonal Transport, Gene Expression Regulation, Developmental, Protein Transport, Neurogenesis, Kinesins
Depositing User: Symplectic Admin
Date Deposited: 27 Jun 2017 09:59
Last Modified: 19 Jan 2023 07:05
DOI: 10.7554/eLife.14694.001
Open Access URL: https://elifesciences.org/articles/14694
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3007151

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