---
_id: '7005'
abstract:
- lang: eng
  text: Activity-dependent bulk endocytosis generates synaptic vesicles (SVs) during
    intense neuronal activity via a two-step process. First, bulk endosomes are formed
    direct from the plasma membrane from which SVs are then generated. SV generation
    from bulk endosomes requires the efflux of previously accumulated calcium and
    activation of the protein phosphatase calcineurin. However, it is still unknown
    how calcineurin mediates SV generation. We addressed this question using a series
    of acute interventions that decoupled the generation of SVs from bulk endosomes
    in rat primary neuronal culture. This was achieved by either disruption of protein–protein
    interactions via delivery of competitive peptides, or inhibition of enzyme activity
    by known inhibitors. SV generation was monitored using either a morphological
    horseradish peroxidase assay or an optical assay that monitors the replenishment
    of the reserve SV pool. We found that SV generation was inhibited by, (i) peptides
    that disrupt calcineurin interactions, (ii) an inhibitor of dynamin I GTPase activity
    and (iii) peptides that disrupt the phosphorylation-dependent dynamin I–syndapin
    I interaction. Peptides that disrupted syndapin I interactions with eps15 homology
    domain-containing proteins had no effect. This revealed that (i) calcineurin must
    be localized at bulk endosomes to mediate its effect, (ii) dynamin I GTPase activity
    is essential for SV fission and (iii) the calcineurin-dependent interaction between
    dynamin I and syndapin I is essential for SV generation. We therefore propose
    that a calcineurin-dependent dephosphorylation cascade that requires both dynamin
    I GTPase and syndapin I lipid-deforming activity is essential for SV generation
    from bulk endosomes.
article_processing_charge: No
article_type: original
author:
- first_name: Giselle T
  full_name: Cheung, Giselle T
  id: 471195F6-F248-11E8-B48F-1D18A9856A87
  last_name: Cheung
  orcid: 0000-0001-8457-2572
- first_name: Michael A.
  full_name: Cousin, Michael A.
  last_name: Cousin
citation:
  ama: Cheung GT, Cousin MA. Synaptic vesicle generation from activity‐dependent bulk
    endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction.
    <i>Journal of Neurochemistry</i>. 2019;151(5):570-583. doi:<a href="https://doi.org/10.1111/jnc.14862">10.1111/jnc.14862</a>
  apa: Cheung, G. T., &#38; Cousin, M. A. (2019). Synaptic vesicle generation from
    activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin
    interaction. <i>Journal of Neurochemistry</i>. Wiley. <a href="https://doi.org/10.1111/jnc.14862">https://doi.org/10.1111/jnc.14862</a>
  chicago: Cheung, Giselle T, and Michael A. Cousin. “Synaptic Vesicle Generation
    from Activity‐dependent Bulk Endosomes Requires a Dephosphorylation‐dependent
    Dynamin–Syndapin Interaction.” <i>Journal of Neurochemistry</i>. Wiley, 2019.
    <a href="https://doi.org/10.1111/jnc.14862">https://doi.org/10.1111/jnc.14862</a>.
  ieee: G. T. Cheung and M. A. Cousin, “Synaptic vesicle generation from activity‐dependent
    bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction,”
    <i>Journal of Neurochemistry</i>, vol. 151, no. 5. Wiley, pp. 570–583, 2019.
  ista: Cheung GT, Cousin MA. 2019. Synaptic vesicle generation from activity‐dependent
    bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction.
    Journal of Neurochemistry. 151(5), 570–583.
  mla: Cheung, Giselle T., and Michael A. Cousin. “Synaptic Vesicle Generation from
    Activity‐dependent Bulk Endosomes Requires a Dephosphorylation‐dependent Dynamin–Syndapin
    Interaction.” <i>Journal of Neurochemistry</i>, vol. 151, no. 5, Wiley, 2019,
    pp. 570–83, doi:<a href="https://doi.org/10.1111/jnc.14862">10.1111/jnc.14862</a>.
  short: G.T. Cheung, M.A. Cousin, Journal of Neurochemistry 151 (2019) 570–583.
date_created: 2019-11-12T14:37:08Z
date_published: 2019-12-01T00:00:00Z
date_updated: 2023-08-30T07:21:50Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1111/jnc.14862
external_id:
  isi:
  - '000490703100001'
  pmid:
  - '31479508'
file:
- access_level: open_access
  checksum: ec1fb2aebb874009bc309adaada6e1d7
  content_type: application/pdf
  creator: dernst
  date_created: 2020-02-05T10:30:02Z
  date_updated: 2020-07-14T12:47:47Z
  file_id: '7452'
  file_name: 2019_JournNeurochemistry_Cheung.pdf
  file_size: 4334962
  relation: main_file
file_date_updated: 2020-07-14T12:47:47Z
has_accepted_license: '1'
intvolume: '       151'
isi: 1
issue: '5'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 570-583
pmid: 1
publication: Journal of Neurochemistry
publication_identifier:
  eissn:
  - 1471-4159
  issn:
  - 0022-3042
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Synaptic vesicle generation from activity‐dependent bulk endosomes requires
  a dephosphorylation‐dependent dynamin–syndapin interaction
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 151
year: '2019'
...