McInnes, J;
Wierda, K;
Snellinx, A;
Bounti, L;
Wang, Y-C;
Stancu, I-C;
Apóstolo, N;
... Verstreken, P; + view all
(2018)
Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau.
Neuron
, 97
(4)
823-835.e8.
10.1016/j.neuron.2018.01.022.
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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.
| Type: | Article |
|---|---|
| Title: | Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neuron.2018.01.022 |
| Publisher version: | https://doi.org/10.1016/j.neuron.2018.01.022 |
| Language: | English |
| Additional information: | © 2018 Elsevier Inc. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Alzheimer’s disease, Synaptogyrin-3, Syngr3, Tau, Tauopathy, neurodegeneration, presynapse, synapse, synaptic dysfunction, synaptic vesicles |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UK Dementia Research Institute HQ |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10043358 |
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