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- W4321482821 abstract "The neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. NFs are highly dynamic, and the regulation of NF assembly state is incompletely understood. Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. We identify five NF-L O-GlcNAc sites and show that they regulate NF assembly state. Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. We further show that NF-L O-GlcNAcylation is required for normal organelle trafficking in primary neurons, underlining its functional significance. Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. Our results demonstrate that site-specific glycosylation regulates NF-L assembly and function, and aberrant NF O-GlcNAcylation may contribute to CMT and other neurodegenerative disorders." @default.
- W4321482821 created "2023-02-23" @default.
- W4321482821 creator A5004519371 @default.
- W4321482821 creator A5023584756 @default.
- W4321482821 creator A5034926402 @default.
- W4321482821 creator A5053884492 @default.
- W4321482821 creator A5054443109 @default.
- W4321482821 creator A5055915667 @default.
- W4321482821 creator A5059827125 @default.
- W4321482821 creator A5078062014 @default.
- W4321482821 creator A5091199932 @default.
- W4321482821 date "2023-02-22" @default.
- W4321482821 modified "2023-09-26" @default.
- W4321482821 title "O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations" @default.
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