PMID: 8702840

 

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

Abstract :

1. Neurofilaments, the major intermediate filaments in large myelinated neurons, are essential for specifying proper axonal caliber
2. 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
3. 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
4. Chem
5. 268, 16679-16687)
6. 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 approximately 50 KSP repeats
7. 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
8. 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