---
_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.
Journal of Neurochemistry. 2019;151(5):570-583. doi:10.1111/jnc.14862
apa: Cheung, G. T., & Cousin, M. A. (2019). Synaptic vesicle generation from
activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin
interaction. Journal of Neurochemistry. Wiley. https://doi.org/10.1111/jnc.14862
chicago: Cheung, Giselle T, and Michael A. Cousin. “Synaptic Vesicle Generation
from Activity‐dependent Bulk Endosomes Requires a Dephosphorylation‐dependent
Dynamin–Syndapin Interaction.” Journal of Neurochemistry. Wiley, 2019.
https://doi.org/10.1111/jnc.14862.
ieee: G. T. Cheung and M. A. Cousin, “Synaptic vesicle generation from activity‐dependent
bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction,”
Journal of Neurochemistry, 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.” Journal of Neurochemistry, vol. 151, no. 5, Wiley, 2019,
pp. 570–83, doi:10.1111/jnc.14862.
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'
...