Cytoplasmic O-GlcNAc modification of the head domain and the KSP repeat motif of the neurofilament protein neurofilament-H

Dennis L Y Dong, Zuo Shang Xu, Gerald Warren Hart, Don W. Cleveland

Research output: Contribution to journalArticle

Abstract

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 tall 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.

Original languageEnglish (US)
Pages (from-to)20845-20852
Number of pages8
JournalJournal of Biological Chemistry
Volume271
Issue number34
DOIs
StatePublished - 1996

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Neurofilament Proteins
Phosphorylation
Intermediate Filaments
Head
Acetylglucosamine
Neurons
Peptides
neurofilament protein H

ASJC Scopus subject areas

  • Biochemistry

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Cytoplasmic O-GlcNAc modification of the head domain and the KSP repeat motif of the neurofilament protein neurofilament-H. / Dong, Dennis L Y; Xu, Zuo Shang; Hart, Gerald Warren; Cleveland, Don W.

In: Journal of Biological Chemistry, Vol. 271, No. 34, 1996, p. 20845-20852.

Research output: Contribution to journalArticle

Dong, Dennis L Y ; Xu, Zuo Shang ; Hart, Gerald Warren ; Cleveland, Don W. / Cytoplasmic O-GlcNAc modification of the head domain and the KSP repeat motif of the neurofilament protein neurofilament-H. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 34. pp. 20845-20852.
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