Abstract
BackgroundCell surface glycosylation patterns are markers of cell type and status. However, the mechanisms regulating surface glycosylation patterns remain unknown.Methodology/Principal FindingsUsing a panel of carbohydrate surface markers, we have shown that cell surface sialylation and fucosylation were downregulated in L1−/y neurons versus L1+/y neurons. Consistently, mRNA levels of sialyltransferase ST6Gal1, and fucosyltransferase FUT9 were significantly reduced in L1−/y neurons. Moreover, treatment of L1+/y neurons with L1 antibodies, triggering signal transduction downstream of L1, led to an increase in cell surface sialylation and fucosylation compared to rat IgG-treated cells. ShRNAs for both ST6Gal1 and FUT9 blocked L1 antibody-mediated enhancement of neurite outgrowth, cell survival and migration. A phospholipase Cγ (PLCγ) inhibitor and shRNA, as well as an Erk inhibitor, reduced ST6Gal1 and FUT9 mRNA levels and inhibited effects of L1 on neurite outgrowth and cell survival.ConclusionsNeuronal surface sialylation and fucosylation are regulated via PLCγ by L1, modulating neurite outgrowth, cell survival and migration.
Highlights
Glycosylation of proteins and lipids is a prime example of a cellular process that is not under the direct control of the genome
Neuronal surface sialylation and fucosylation are regulated via phospholipase Cc (PLCc) by L1, modulating neurite outgrowth, cell survival and migration
The quantitative results showed that the expression of a2,6-linked sialic acid, a2,3-linked sialic acid, fucose, and Nacetyllactosamin in complex and hybrid sugars as well as LewisX were significantly downregulated in neurons of L12/y mice compared with L1+/y neurons (Fig. 1A)
Summary
Glycosylation of proteins and lipids is a prime example of a cellular process that is not under the direct control of the genome. This contributes to the functional diversity required to generate extensive phenotypes from a limited genotype [1]. Glycosylation is a crucial post- or co-translational modification of more than 50% of all eukaryotic proteins according to database analyses [2]. It is affected by a multitude of factors, such as cellular metabolism and the rate of cell growth.
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