---
_id: '472'
abstract:
- lang: eng
  text: 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.
author:
- first_name: Kohgaku
  full_name: Eguchi, Kohgaku
  id: 2B7846DC-F248-11E8-B48F-1D18A9856A87
  last_name: Eguchi
  orcid: 0000-0002-6170-2546
- first_name: Zachari
  full_name: Taoufiq, Zachari
  last_name: Taoufiq
- first_name: Oliver
  full_name: Thorn Seshold, Oliver
  last_name: Thorn Seshold
- first_name: Dirk
  full_name: Trauner, Dirk
  last_name: Trauner
- first_name: Masato
  full_name: Hasegawa, Masato
  last_name: Hasegawa
- first_name: Tomoyuki
  full_name: Takahashi, Tomoyuki
  last_name: Takahashi
citation:
  ama: 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. <i>European Journal of Neuroscience</i>.
    2017;37(25):6043-6052. doi:<a href="https://doi.org/10.1523/JNEUROSCI.0179-17.2017">10.1523/JNEUROSCI.0179-17.2017</a>
  apa: Eguchi, K., Taoufiq, Z., Thorn Seshold, O., Trauner, D., Hasegawa, M., &#38;
    Takahashi, T. (2017). Wild-type monomeric α-synuclein can impair vesicle endocytosis
    and synaptic fidelity via tubulin polymerization at the calyx of held. <i>European
    Journal of Neuroscience</i>. Wiley-Blackwell. <a href="https://doi.org/10.1523/JNEUROSCI.0179-17.2017">https://doi.org/10.1523/JNEUROSCI.0179-17.2017</a>
  chicago: 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.” <i>European Journal of Neuroscience</i>. Wiley-Blackwell, 2017. <a href="https://doi.org/10.1523/JNEUROSCI.0179-17.2017">https://doi.org/10.1523/JNEUROSCI.0179-17.2017</a>.
  ieee: 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,” <i>European Journal of Neuroscience</i>,
    vol. 37, no. 25. Wiley-Blackwell, pp. 6043–6052, 2017.
  ista: 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.
  mla: Eguchi, Kohgaku, et al. “Wild-Type Monomeric α-Synuclein Can Impair Vesicle
    Endocytosis and Synaptic Fidelity via Tubulin Polymerization at the Calyx of Held.”
    <i>European Journal of Neuroscience</i>, vol. 37, no. 25, Wiley-Blackwell, 2017,
    pp. 6043–52, doi:<a href="https://doi.org/10.1523/JNEUROSCI.0179-17.2017">10.1523/JNEUROSCI.0179-17.2017</a>.
  short: K. Eguchi, Z. Taoufiq, O. Thorn Seshold, D. Trauner, M. Hasegawa, T. Takahashi,
    European Journal of Neuroscience 37 (2017) 6043–6052.
date_created: 2018-12-11T11:46:40Z
date_published: 2017-06-21T00:00:00Z
date_updated: 2021-01-12T08:00:51Z
day: '21'
doi: 10.1523/JNEUROSCI.0179-17.2017
extern: '1'
intvolume: '        37'
issue: '25'
language:
- iso: eng
month: '06'
oa_version: None
page: 6043 - 6052
publication: European Journal of Neuroscience
publication_identifier:
  issn:
  - '02706474'
publication_status: published
publisher: Wiley-Blackwell
publist_id: '7348'
quality_controlled: '1'
status: public
title: Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic
  fidelity via tubulin polymerization at the calyx of held
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 37
year: '2017'
...