Two protein N-acetylgalactosaminyl transferases regulate synaptic plasticity by activity-dependent regulation of integrin signaling.

Dani N, Zhu H, Broadie K
J Neurosci. 2014 34 (39): 13047-65

PMID: 25253852 · PMCID: PMC4172800 · DOI:10.1523/JNEUROSCI.1484-14.2014

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.

Copyright © 2014 the authors 0270-6474/14/3413047-19$15.00/0.

MeSH Terms (10)

Animals Drosophila Drosophila Proteins Integrin alpha Chains N-Acetylgalactosaminyltransferases Neuromuscular Junction Neuronal Plasticity Synaptic Transmission Synaptic Vesicles Tenascin

Connections (2)

This publication is referenced by other Labnodes entities:

Links