Two Protein N-acetylgalactosaminyl Transferases Regulate Synaptic Plasticity by Activity-dependent Regulation of Integrin Signaling

Overview

Journal J Neurosci

Specialty Neurology

Date 2014 Sep 26

PMID 25253852

Citations 20

Authors

Neil Dani

He Zhu

Kendal Broadie

Affiliations

Soon will be listed here.

Abstract

Using a Drosophila whole-genome transgenic RNAi screen for glycogenes regulating synapse function, we have identified two protein α-N-acetylgalactosaminyltransferases (pgant3 and pgant35A) that regulate synaptic O-linked glycosylation (GalNAcα1-O-S/T). Loss of either pgant alone elevates presynaptic/postsynaptic molecular assembly and evoked neurotransmission strength, but synapses appear restored to normal in double mutants. Likewise, activity-dependent facilitation, augmentation, and posttetanic potentiation are all suppressively impaired in pgant mutants. In non-neuronal contexts, pgant function regulates integrin signaling, and we show here that the synaptic Position Specific 2 (αPS2) integrin receptor and transmembrane tenascin ligand are both suppressively downregulated in pgant mutants. Channelrhodopsin-driven activity rapidly (<1 min) drives integrin signaling in wild-type synapses but is suppressively abolished in pgant mutants. Optogenetic stimulation in pgant mutants alters presynaptic vesicle trafficking and postsynaptic pocket size during the perturbed integrin signaling underlying synaptic plasticity defects. Critically, acute blockade of integrin signaling acts synergistically with pgant mutants to eliminate all activity-dependent synaptic plasticity.

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