TY - JOUR
T1 - Cell surface sialylation and fucosylation are regulated by L1 via phospholipase Cgamma and cooperate to modulate neurite outgrowth, cell survival and migration
AU - Li, Ya-li
AU - Wu, Guang-zhi
AU - Dawe, Gavin S
AU - Zeng, Li
AU - Cui, Shu-sen
AU - Loers, Gabriele
AU - Tilling, Thomas
AU - Sun, Li
AU - Schachner, Melitta
AU - Xiao, Zhi-Cheng
PY - 2008
Y1 - 2008
N2 - BACKGROUND: Cell surface glycosylation patterns are markers of cell type and status. However, the mechanisms regulating surface glycosylation patterns remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using 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 Cgamma (PLCgamma) 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. CONCLUSIONS: Neuronal surface sialylation and fucosylation are regulated via PLCgamma by L1, modulating neurite outgrowth, cell survival and migration.
AB - BACKGROUND: Cell surface glycosylation patterns are markers of cell type and status. However, the mechanisms regulating surface glycosylation patterns remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using 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 Cgamma (PLCgamma) 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. CONCLUSIONS: Neuronal surface sialylation and fucosylation are regulated via PLCgamma by L1, modulating neurite outgrowth, cell survival and migration.
UR - http://www.scopus.com/record/display.url?eid=2-s2.0-57349171403&origin=inward&txGid=n-WOVf_1I2CffHwColPcQhh%3a11
U2 - 10.1371/journal.pone.0003841
DO - 10.1371/journal.pone.0003841
M3 - Article
SN - 1932-6203
VL - 3
SP - 1
EP - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 12
ER -