Core-N-glycans are atypically abundant at the neuronal surface and regulate glutamate receptor signaling
Year: 2024
Type: preprint
Abstract: Neurotransmitter receptors, like most surface proteins, are extensively modified by covalent addition of N-glycans during their synthesis. Surprisingly, the most abundant N-glycans in the mammalian brain are core-glycans, sugars that typically earmark immature intracellular proteins in non-neuronal cells. The function of these glycans in neurons is yet largely unknown. To address this, we combined conditional gene knockout, mass spectrometry, quantitative imaging and electrophysiological recordings in cultured neurons and brain slices. We show that core-glycans are expressed at high levels at the neuronal surface, indicating expression on functional proteins. Focusing on excitatory synapses, we found that core-glycans reduce dendritic spine density and synaptic AMPA receptor expression but are overall sufficient to sustain functional synapses. Our results indicate that core-glycans slow the desensitization of AMPA receptor complexes and reduce NMDA receptor signaling at synapses. Core-glycans hence impair NMDA receptor-dependent synaptic plasticity, unraveling a previously unrecognized role for N-glycosylation in regulating synaptic composition and transmission efficacy.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Dual N-glycosylation of AMPA receptors and impact on synaptic transmission and plasticity, Emergence of inhibitory plasticities in hippocampal area CA2 underlying normal and pathological develpment of social memory during adolescence, G3347568920, G4656594441, G5365145810, Unconventional N-Glycosylation and Diversification of Neuronal Ion Channel Properties
OpenAlex ID: W4393227252