title: O-GlcNAc transferase regulates excitatory synapse maturity.
abstract: Experience-driven synaptic plasticity is believed to underlie adaptive behavior by rearranging the way neuronal circuits process information. We have previously discovered that O-GlcNAc transferase (OGT), an enzyme that modifies protein function by attaching β-N-acetylglucosamine (GlcNAc) to serine and threonine residues of intracellular proteins (O-GlcNAc), regulates food intake by modulating excitatory synaptic function in neurons in the hypothalamus. However, how OGT regulates excitatory synapse function is largely unknown. Here we demonstrate that OGT is enriched in the postsynaptic density of excitatory synapses. In the postsynaptic density, O-GlcNAcylation on multiple proteins increased upon neuronal stimulation. Knockout of the OGT gene decreased the synaptic expression of the AMPA receptor GluA2 and GluA3 subunits, but not the GluA1 subunit. The number of opposed excitatory presynaptic terminals was sharply reduced upon postsynaptic knockout of OGT. There were also fewer and less mature dendritic spines on OGT knockout neurons. These data identify OGT as a molecular mechanism that regulates synapse maturity.
authors.affiliation: Solomon H. Snyder Department of Neuroscience and Kavli Neuroscience Discovery Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.|Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Olof
authors.initials: O
authors.lastname: Lagerlöf
authors.affiliation: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Hart
authors.affiliation: Solomon H. Snyder Department of Neuroscience and Kavli Neuroscience Discovery Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; rhuganir@jhmi.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C104722:glutamate receptor ionotropic, AMPA 2
keywords: AMPA receptors; O-GlcNAc; OGT; excitatory synapses