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). ISSN 2050-084X

Text Voelzmann et all 13.7.2016 .pdf - Author Accepted Manuscript Download (36MB)

Abstract

© Voelzmann et al.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
Depositing User:	Symplectic Admin
Date Deposited:	13 Sep 2016 10:50
Last Modified:	19 Jan 2023 07:30
DOI:	10.7554/eLife.14694.001
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3003282