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Abstract:
Like most membrane proteins, neurotransmitter receptors (NTRs) are extensively modified by covalently attached N-glycans. Despite a general awareness that N-glycans may significantly diversify the structure and activity of these proteins, surprisingly little is known about the impact of N-glycosylation on synaptic transmission. As a result of unconventional secretory trafficking, we found that many nascent synaptic proteins processed in neuronal protrusions bypass the central Golgi apparatus located in the neuronal cell body and hence acquire core-glycosylated profiles that are atypical for mature surface proteins. Focusing on glutamate receptors, our recent work shows that the acquisition of either core- or complex N-glycosylation profiles regulates NTR surface dynamics, membrane compartmentalisation and signalling at synapses. Our findings hence unravel a previously unrecognised role for N-glycosylation in regulating synaptic composition and transmission efficacy, opening new vistas to understand how N-glycans regulate neuronal function and plasticity in health and disease.

key words: local protein synthesis, synaptic plasticity, membrane trafficking, single molecule imaging, genetic engineering