Cytoplasmic O-GlcNAc Modification of the Head Domain and the KSP Repeat Motif of the Neurofilament Protein Neurofilament-H

Neurofilaments, the major intermediate filaments in large myelinated neurons, are essential for specifying proper axonal caliber. Mammalian neurofilaments are obligate heteropolymers assembled from three polypeptides, neurofilament (NF)-H, NF-M, and NF-L, each of which undergoes phosphorylation at m...

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Bibliographic Details
Published in:The Journal of biological chemistry 1996-08, Vol.271 (34), p.20845-20852
Main Authors: Dong, Dennis L.-Y., Xu, Zuo-Shang, Hart, Gerald W., Cleveland, Don W.
Format: Article
Language:English
Subjects:
Acetylglucosamine - metabolism
Amino Acid Sequence
Animals
Glycopeptides - chemistry
Glycosylation
Male
Molecular Sequence Data
Nerve Tissue Proteins - chemistry
Neurofilament Proteins - chemistry
Neurofilament Proteins - metabolism
Peptide Mapping
Protein Processing, Post-Translational
Rats
Repetitive Sequences, Nucleic Acid
Serine - chemistry
Spinal Cord - chemistry
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Summary:Neurofilaments, the major intermediate filaments in large myelinated neurons, are essential for specifying proper axonal caliber. Mammalian neurofilaments are obligate heteropolymers assembled from three polypeptides, neurofilament (NF)-H, NF-M, and NF-L, each of which undergoes phosphorylation at multiple sites. NF-M and NF-L are known to be modified by O-linked N-acetylglucosamine (O-GlcNAc) (Dong, D. L.-Y., Xu, Z.-S., Chevrier, M. R., Cotter, R. J., Cleveland, D. W., and Hart, G. W. (1993) J. Biol. Chem. 268, 16679-16687). Here we further report that NF-H is extensively modified by O-GlcNAc at Thr53, Ser54, and Ser56 in the head domain and, somewhat surprisingly, at multiple sites within the Lys-Ser-Pro repeat motif in the tail domain, a region in assembled neurofilaments known to be nearly stoichiometrically phosphorylated on each of the ∼50 KSP repeats. Beyond the earlier identified sites on NF-M and NF-L, O-GlcNAc sites on Thr19 and Ser34 of NF-M and Ser34 and Ser48 of NF-L are also determined here, all of which are localized in head domain sequences critical for filament assembly. The proximity of O-GlcNAc and phosphorylation sites in both head and tail domains of each subunit indicates that these modifications may influence one another and play a role in filament assembly and network formation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.271.34.20845