McInnes J, Wierda K, Snellinx A, Bounti L, Wang YC, Stancu IC, Apóstolo N, Gevaert K, Dewachter I, Spires-Jones TL, De Strooper B, De Wit J, Zhou L, Verstreken P. Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau. Neuron. 2018 Feb 21;97(4):823-835.e8. Epub 2018 Feb 1 PubMed.

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  1. The study by McInnes et al., together with a previous study from the same group (Zhou et al., 2017), suggests a very interesting mechanism of tau-mediated neurotoxicity. The proposed mechanism is based on a direct interaction of tau with synaptic vesicles, which cross-links synaptic vesicles with filamentous actin and thus affects the mobility of synaptic vesicles at presynaptic compartments. In this new study, a transmembrane protein is identified that mediates the interaction between tau and synaptic vesicles and thus could be an important player in tau-mediated neurotoxicity. The identified transmembrane protein is synaptogyrin-3, a member of the family of tetraspanin vesicle proteins. Tetraspanin vesicle proteins are highly abundant components of synaptic vesicles. Little is known, however, about their function. Given the potentially important role of a direct interaction between tau and synaptogyrin-3, it will be important to understand this interaction at the molecular level, in particular in context of the three-dimensional structure of tetraspanin vesicle proteins, which is still enigmatic.

    References:

    Zhou L, McInnes J, Wierda K, Holt M, Herrmann AG, Jackson RJ, Wang YC, Swerts J, Beyens J, Miskiewicz K, Vilain S, Dewachter I, Moechars D, De Strooper B, Spires-Jones TL, De Wit J, Verstreken P. Tau association with synaptic vesicles causes presynaptic dysfunction. Nat Commun. 2017 May 11;8:15295. PubMed.

    View all comments by Markus Zweckstetter

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