Header

UZH-Logo

Maintenance Infos

Dysbindin links presynaptic proteasome function to homeostatic recruitment of low release probability vesicles


Wentzel, Corinna; Delvendahl, Igor; Sydlik, Sebastian; Georgiev, Oleg; Müller, Martin (2018). Dysbindin links presynaptic proteasome function to homeostatic recruitment of low release probability vesicles. Nature Communications:9:267.

Abstract

Here we explore the relationship between presynaptic homeostatic plasticity and proteasome function at the Drosophila neuromuscular junction. First, we demonstrate that the induction of homeostatic plasticity is blocked after presynaptic proteasome perturbation. Proteasome inhibition potentiates release under baseline conditions but not during homeostatic plasticity, suggesting that proteasomal degradation and homeostatic plasticity modulate a common pool of vesicles. The vesicles that are regulated by proteasome function and recruited during homeostatic plasticity are highly EGTA sensitive, implying looser Ca2+ influx-release coupling. Similar to homeostatic plasticity, proteasome perturbation enhances presynaptic Ca2+ influx, readily-releasable vesicle pool size, and does not potentiate release after loss of specific homeostatic plasticity genes, including the schizophrenia-susceptibility gene dysbindin. Finally, we provide genetic evidence that Dysbindin levels regulate the access to EGTA-sensitive vesicles. Together, our data suggest that presynaptic protein degradation opposes the release of low-release probability vesicles that are potentiated during homeostatic plasticity and whose access is controlled by dysbindin.

Abstract

Here we explore the relationship between presynaptic homeostatic plasticity and proteasome function at the Drosophila neuromuscular junction. First, we demonstrate that the induction of homeostatic plasticity is blocked after presynaptic proteasome perturbation. Proteasome inhibition potentiates release under baseline conditions but not during homeostatic plasticity, suggesting that proteasomal degradation and homeostatic plasticity modulate a common pool of vesicles. The vesicles that are regulated by proteasome function and recruited during homeostatic plasticity are highly EGTA sensitive, implying looser Ca2+ influx-release coupling. Similar to homeostatic plasticity, proteasome perturbation enhances presynaptic Ca2+ influx, readily-releasable vesicle pool size, and does not potentiate release after loss of specific homeostatic plasticity genes, including the schizophrenia-susceptibility gene dysbindin. Finally, we provide genetic evidence that Dysbindin levels regulate the access to EGTA-sensitive vesicles. Together, our data suggest that presynaptic protein degradation opposes the release of low-release probability vesicles that are potentiated during homeostatic plasticity and whose access is controlled by dysbindin.

Statistics

Citations

Altmetrics

Downloads

4 downloads since deposited on 01 Feb 2018
4 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:18 January 2018
Deposited On:01 Feb 2018 12:27
Last Modified:18 Apr 2018 11:49
Publisher:Nature Publishing Group
ISSN:2041-1723
Funders:SNF
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41467-017-02494-0
Project Information:
  • : FunderSNSF
  • : Grant ID
  • : Project TitleSNF

Download

Download PDF  'Dysbindin links presynaptic proteasome function to homeostatic recruitment of low release probability vesicles'.
Preview
Content: Published Version
Filetype: PDF
Size: 4MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)