Branching of O-mannose glycans regulates node of Ranvier organization and saltatory conduction.

Authors

Shu Tomita, Taichi Nakaishi, Toshiyuki Ishii, Kazuya Ono, Honoka Fujimori, Misuzu Hashimoto, Shiho Ohno, Yoshiki Yamaguchi, Masamitsu Shimazawa, Miyako Nakano, Daisuke Kato, Yasuhiko Kizuka

Published in

Communications biology. Volume 9. Issue 1. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

The myelin sheath of axons is organized into domain structures with nodes of Ranvier that facilitate saltatory conduction. Here, we show that a brain-specific glycosyltransferase, MGAT5B that catalyzes β1,6-GlcNAc branching of an O-mannose (Man) glycan, is required for node of Ranvier integrity. Mgat5b knockout (KO) mice displayed broadening of nodes in brain white matter. Consistently, electrophysiological analysis demonstrated a significant delay and variable axonal conduction in Mgat5b KO mice, indicating the importance of branched O-Man glycans in node morphology and functions. Biochemical and glycoproteomic analyses demonstrated that MGAT5B modifies the glycans of a key node-organizing glycoprotein, neurofascin 186 (NF186), and that interaction between NF186 and Contactin 1 is negatively regulated by branched O-Man glycans. Finally, neuron-specific restoration of MGAT5B in KO mice rescued these nodal defects, indicating a cell-autonomous role of MGAT5B in node organization. Our findings highlight a glycan-mediated mechanism for the maintenance of node structure and function.

PMID:
42443397
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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