Cell surface sialylation and fucosylation are regulated by L1 via phospholipase Cgamma and cooperate to modulate neurite outgrowth, cell survival and migration.
BACKGROUND
Cell surface glycosylation patterns are markers of cell type and status. However, the mechanisms regulating surface glycosylation patterns remain unknown.


RESULTS
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.
Li
Ya-Li
YL
Department of Anatomy, Research Centre of Heart, Brain, Hormone and Healthy Aging, and the State Laboratory of Brain and Cognitive Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Wu
Guang-Zhi
GZ
Dawe
Gavin S
GS
Zeng
Li
L
Cui
Shu-Sen
SS
Loers
Gabriele
G
Tilling
Thomas
T
Sun
Li
L
Schachner
Melitta
M
Xiao
Zhi-Cheng
ZC
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D051966:Phospholipase C gamma / Q000378:metabolism*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D039842:Neural Cell Adhesion Molecule L1; D005647:Fucosyltransferases; C518194:fucosyltransferase 9, mouse; D012799:Sialyltransferases; D051966:Phospholipase C gamma; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase