| First Author | Benner O | Year | 2023 |
| Journal | J Biol Chem | Volume | 299 |
| Issue | 12 | Pages | 105361 |
| PubMed ID | 37865312 | Mgi Jnum | J:343246 |
| Mgi Id | MGI:7563395 | Doi | 10.1016/j.jbc.2023.105361 |
| Citation | Benner O, et al. (2023) Multiple N-linked glycosylation sites critically modulate the synaptic abundance of neuroligin isoforms. J Biol Chem 299(12):105361 |
| abstractText | In recent years, elegant glycomic and glycoproteomic approaches have revealed an intricate glycosylation profile of mammalian brain with enormous spatial and temporal diversities. Nevertheless, at a cellular level, it is unclear how these post-translational modifications affect various proteins to influence crucial neuronal properties. Here, we have investigated the impact of N-linked glycosylation on neuroligins (NLGNs), a class of cell-adhesion molecules that play instructive roles in synapse organization. We found that endogenous NLGN proteins are differentially glycosylated across several regions of murine brain in a sex-independent but isoform-dependent manner. In both rodent primary neurons derived from brain sections and human neurons differentiated from stem cells, all NLGN variants were highly enriched with multiple N-glycan subtypes, which cumulatively ensured their efficient trafficking to the cell surface. Removal of these N-glycosylation residues only had a moderate effect on NLGNs' stability or expression levels but particularly enhanced their retention at the endoplasmic reticulum. As a result, the glycosylation-deficient NLGNs exhibited considerable impairments in their dendritic distribution and postsynaptic accumulation, which in turn, virtually eliminated their ability to recruit presynaptic terminals and significantly reduced NLGN overexpression-induced assemblies of both glutamatergic and GABAergic synapse structures. Therefore, our results highlight an essential mechanistic contribution of N-linked glycosylations in facilitating the appropriate secretory transport of a major synaptic cell-adhesion molecule and promoting its cellular function in neurons. |
