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Title: Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau
Authors: McInnes, Joseph
Wierda, Keimpe
Snellinx, An
Bounti, Laura
Wang, Yu-Chun
Stancu, Ilie-Cosmin 
Apostolo, Nuno
Gevaert, Kris
Dewachter, Ilse 
Spires-Jones, Tara L.
De Strooper, Bart
De Wit, Joris
Zhou, Lujia
Verstreken, Patrik
Issue Date: 2018
Source: NEURON, 97(4), p. 823-835
Abstract: Synaptic dysfunction is an early pathological feature of neurodegenerative diseases associated with Tau, including Alzheimer's disease. Interfering with early synaptic dysfunction may be therapeutically beneficial to prevent cognitive decline and disease progression, but the mechanisms underlying synaptic defects associated with Tau are unclear. In disease conditions, Tau mislocalizes into pre- and postsynaptic compartments; here we show that, under pathological conditions, Tau binds to presynaptic vesicles in Alzheimer's disease patient brain. We define that the binding of Tau to synaptic vesicles is mediated by the transmembrane vesicle protein Synaptogyrin-3. In fly and mouse models of Tauopathy, reduction of Synaptogyrin-3 prevents the association of presynaptic Tau with vesicles, alleviates Tau-induced defects in vesicle mobility, and restores neurotransmitter release. This work therefore identifies Synaptogyrin-3 as the binding partner of Tau on synaptic vesicles, revealing a new presynapse-specific Tau interactor, which may contribute to early synaptic dysfunction in neurodegenerative diseases associated with Tau.
Notes: Verstreken, P (reprint author), VIB KU Leuven Ctr Brain & Dis Res, B-3000 Leuven, Belgium,
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ISSN: 0896-6273
e-ISSN: 1097-4199
DOI: 10.1016/j.neuron.2018.01.022
ISI #: 000425713200011
Category: A1
Type: Journal Contribution
Validations: ecoom 2019
Appears in Collections:Research publications

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