EXPRESSION OF THE BETA-GALACTOSIDE ALPHA-1,2-FUCOSYL-TRANSFERASE GENESUPPRESSES AXONAL OUTGROWTH OF NEURO2A NEUROBLASTOMA-CELLS

The axonal outgrowth of cells of Neuro2a, a mouse neuroblastoma cell l ine, was suppressed on expression of the beta-galactoside alpha 1,2-fu cosyltransferase (alpha 1,2-FT) gene. We recently cloned two types of rabbit alpha 1,2-FT, RFT-I and RFT-II, RFT-I exhibits comparable kinet ic properties and structural homology with human H gene alpha 1,2-FT, and RFT-II shows comparable kinetic parameters with human Se gene alph a 1,2-FT. Neuro2a cells expressing RFT-I (N2A-RFT-I) contained a large amount of fucosyl GM1 instead of GM1 and GD1a, major gangliosides in the parent Neuro2a cells, whereas Neuro2a cells expressing RFT-II (N2A -RFT-II) showed a subtle change in the ganglioside pattern, N2A-RFT-II and parent Neuro2a cells showed axonal outgrowth in serum-free medium on the exogenous addition of GM1, whereas N2A-RFT-I cells exhibited m ultiple neurite sprouts but not axonal outgrowth. This phenotype was f ully recovered by N2A-RFT-I cells on the addition of D-threo-1-phenyl- 2-decanoylam ino-3-morpholino-1-propanol and alpha-L-fucosidase to the culture medium, which resulted in pronounced reduction of fucosyl GM1 expression. These results suggested that expression of H-type alpha 1 ,2-FT, and subsequent incorporation of fucose into glycolipids and gly coproteins, especially the formation of fucosyl GM1, modifies the resp onse of neuronal cells to stimuli that induce axonal extension.