Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic fidelity via tubulin polymerization at the calyx of held

K. Eguchi, Z. Taoufiq, O. Thorn Seshold, D. Trauner, M. Hasegawa, T. Takahashi, European Journal of Neuroscience 37 (2017) 6043–6052.

Download
No fulltext has been uploaded. References only!

Journal Article | Published | English
Author
Eguchi, KohgakuIST Austria ; Taoufiq, Zachari; Thorn Seshold, Oliver; Trauner, Dirk; Hasegawa, Masato; Takahashi, Tomoyuki
Abstract
α-Synuclein is a presynaptic protein the function of which has yet to be identified, but its neuronal content increases in patients of synucleinopa-thies including Parkinson’s disease. Chronic overexpression of α-synuclein reportedly expresses various phenotypes of synaptic dysfunction, but the primary target of its toxicity has not been determined. To investigate this, we acutely loaded human recombinant α-synuclein or its pathological mutants in their monomeric forms into the calyces of Held presynaptic terminals in slices from auditorily mature and immature rats of either sex. Membrane capacitance measurements revealed significant and specific inhibitory effects of WT monomeric α-synuclein on vesicle endocytosis throughout development. However, the α-synuclein A53T mutant affected vesicle endocytosis only at immature calyces, where as the A30P mutant had no effect throughout. The endocytic impairment by WTα-synuclein was rescued by intraterminal coloading of the microtubule (MT) polymerization blocker nocodazole. Furthermore, it was reversibly rescued by presynaptically loaded photostatin-1, a pho-toswitcheable inhibitor of MT polymerization, inalight-wavelength-dependent manner. Incontrast, endocyticinhibition by the A53T mutant at immature calyces was not rescued by nocodazole. Functionally, presynaptically loaded WT α-synuclein had no effect on basal synaptic transmission evoked at a low frequency, but significantly attenuated exocytosis and impaired the fidelity of neurotransmission during prolonged high-frequency stimulation. We conclude that monomeric WTα-synuclein primarily inhibits vesicle endocytosis via MT overassembly, thereby impairing high-frequency neurotransmission.
Publishing Year
Date Published
2017-06-21
Journal Title
European Journal of Neuroscience
Volume
37
Issue
25
Page
6043 - 6052
ISSN
IST-REx-ID
472

Cite this

Eguchi K, Taoufiq Z, Thorn Seshold O, Trauner D, Hasegawa M, Takahashi T. Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic fidelity via tubulin polymerization at the calyx of held. European Journal of Neuroscience. 2017;37(25):6043-6052. doi:10.1523/JNEUROSCI.0179-17.2017
Eguchi, K., Taoufiq, Z., Thorn Seshold, O., Trauner, D., Hasegawa, M., & Takahashi, T. (2017). Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic fidelity via tubulin polymerization at the calyx of held. European Journal of Neuroscience, 37(25), 6043–6052. https://doi.org/10.1523/JNEUROSCI.0179-17.2017
Eguchi, Kohgaku, Zachari Taoufiq, Oliver Thorn Seshold, Dirk Trauner, Masato Hasegawa, and Tomoyuki Takahashi. “Wild-Type Monomeric α-Synuclein Can Impair Vesicle Endocytosis and Synaptic Fidelity via Tubulin Polymerization at the Calyx of Held.” European Journal of Neuroscience 37, no. 25 (2017): 6043–52. https://doi.org/10.1523/JNEUROSCI.0179-17.2017.
K. Eguchi, Z. Taoufiq, O. Thorn Seshold, D. Trauner, M. Hasegawa, and T. Takahashi, “Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic fidelity via tubulin polymerization at the calyx of held,” European Journal of Neuroscience, vol. 37, no. 25, pp. 6043–6052, 2017.
Eguchi K, Taoufiq Z, Thorn Seshold O, Trauner D, Hasegawa M, Takahashi T. 2017. Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic fidelity via tubulin polymerization at the calyx of held. European Journal of Neuroscience. 37(25), 6043–6052.
Eguchi, Kohgaku, et al. “Wild-Type Monomeric α-Synuclein Can Impair Vesicle Endocytosis and Synaptic Fidelity via Tubulin Polymerization at the Calyx of Held.” European Journal of Neuroscience, vol. 37, no. 25, Wiley-Blackwell, 2017, pp. 6043–52, doi:10.1523/JNEUROSCI.0179-17.2017.

Export

Marked Publications

Open Data IST Research Explorer

Search this title in

Google Scholar