Dysbindin Links Presynaptic Proteasome Function to Homeostatic Recruitment of Low Release Probability Vesicles

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Jan 20

PMID 29348419

Citations 27

Authors

Corinna Wentzel

Igor Delvendahl

Sebastian Sydlik

Oleg Georgiev

Martin Muller

Affiliations

Soon will be listed here.

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 Ca influx-release coupling. Similar to homeostatic plasticity, proteasome perturbation enhances presynaptic Ca 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.

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