--- res: bibo_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.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Kohgaku foaf_name: Eguchi, Kohgaku foaf_surname: Eguchi foaf_workInfoHomepage: http://www.librecat.org/personId=2B7846DC-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-6170-2546 - foaf_Person: foaf_givenName: Zachari foaf_name: Taoufiq, Zachari foaf_surname: Taoufiq - foaf_Person: foaf_givenName: Oliver foaf_name: Thorn Seshold, Oliver foaf_surname: Thorn Seshold - foaf_Person: foaf_givenName: Dirk foaf_name: Trauner, Dirk foaf_surname: Trauner - foaf_Person: foaf_givenName: Masato foaf_name: Hasegawa, Masato foaf_surname: Hasegawa - foaf_Person: foaf_givenName: Tomoyuki foaf_name: Takahashi, Tomoyuki foaf_surname: Takahashi bibo_doi: 10.1523/JNEUROSCI.0179-17.2017 bibo_issue: '25' bibo_volume: 37 dct_date: 2017^xs_gYear dct_isPartOf: - http://id.crossref.org/issn/02706474 dct_language: eng dct_publisher: Wiley-Blackwell@ dct_title: Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic fidelity via tubulin polymerization at the calyx of held@ ...