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bioRxiv · 10.1101/2023.11.17.567576

N-Glycans on the extracellular domain of the Notch1 receptor control Jagged-1 induced Notch signalling and myogenic differentiation of S100β resident vascular stem cells

Corcoran, E.·Olayinka, A.·Di Luca, M.·Gusti, Y.·Hakimjavadi, R.·O'Connor, B.·Redmond, E. M.·Cahill, P. A.
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Abstract

Notch signalling, critical for development and postnatal homeostasis of the vascular system, is highly regulated by several mechanisms including glycosylation. While the importance of O-linked glycosylation is widely accepted, the structure and function of N-glycans has yet to be defined. Here, we take advantage of lectin binding assays in combination with pharmacological, molecular, and site-directed mutagenetic approaches to study N-glycosylation of the Notch1 receptor. We find that several key oligosaccharides containing bisecting or core fucosylated structures decorate the receptor, control expression and receptor trafficking, and dictate Jagged-1 activation of Notch target genes and myogenic differentiation of multipotent S100{beta} vascular stem cells. N-glycans at asparagine (N) 1241 and 1587 protect the receptor from accelerated degradation, while the oligosaccharide at N888 directly affects signal transduction. Conversely, N-linked glycans at N959, N1179, N1489 do not impact canonical signalling but inhibit differentiation. Our work highlights a novel functional role for N-glycans in controlling Notch1 signalling and differentiation of vascular stem cells. TeaserA sweet development in Notch regulation of vascular smooth muscle cell differentiation

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Corcoran, E., Olayinka, A., Di Luca, M., Gusti, Y., Hakimjavadi, R., O'Connor, B., Redmond, E. M., Cahill, P. A.. 2023-11-17. N-Glycans on the extracellular domain of the Notch1 receptor control Jagged-1 induced Notch signalling and myogenic differentiation of S100β resident vascular stem cells. https://doi.org/10.1101/2023.11.17.567576

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