%0 Journal Article
%T Glycosylation of the Sodium Channel ¦Â4 Subunit is Developmentally Regulated and Involves in Neuritic Degeneration
%A Ting-ting Zhou
%A Zhen-wei Zhang
%A Jun Liu
%A Jian-peng Zhang
%A Bing-hua Jiao
%J International Journal of Biological Sciences
%D 2012
%I Ivyspring International Publisher
%X Aberrant protein glycosylation plays major roles in neurodegenerative diseases, including Parkinson's disease (PD). Glycoproteomics showed that the glycosylation of sodium channel ¦Â4 was significantly increased in human brain tissue. ¦Â4-specific antibodies reacted in immunoblot assays with the 35- and 38-kDa bands from the membrane fractions isolated from neonatal PD transgenic mice but only with the 35-kDa band of the neonatal wild-type mice. The size of the 38-kDa immunoreactive protein is in close agreement with previously reported, suggesting heavy glycosylation of this protein in adult wild-type and neonatal PD transgenic brain tissues. However, the neonatal wild-type mice membrane fractions only contained the 35-kDa immunoreactive protein, and the additional 38-kDa band was not shown until postnatal day 7. Enzymatic deglycosylation of the membrane preparations only converted the 38-kDa band into a faster migrating protein, which was consistent with heavy glycosylation of this protein. The glycosylated state of ¦Â4 was developmentally regulated and was altered in disease state. Neurite outgrowth assay demonstrated that overexpression of deglycosylated mutant ¦Â4-MUT accelerated neurite extension and increased the number of filopodia-like protrusions, when compared with ¦Â4-WT and the vector. These results suggest that extensive glycosylation of ¦Â4 subunit play roles in morphological changes, and the altered glycosylation may be involved in the pathogenesis of PD.
%U http://www.biolsci.org/v08p0630.htm