Influence of monensin on ganglioside anabolism and neurite stability in cultured chick neurons.
We have examined the effects of monensin, a monovalent cationophore that disrupts exo- and endocytosis of membrane vesicles and diminishes Golgi anabolic function, on the incorporation of [3H]-galactose into glycosphingolipids in neurited primary cultures of chick embryo central nervous system neurons. A linear rate of incorporation into all ganglioside species from extracellular-labeled galactose was observed. Specific activity of anabolic labeling was markedly lower in GT1b and GQ1b than in the other major gangliosides of the embryonic neuron (GM3, GD3; GM2, GD2; GM1, GD1a, GD1b). With 100 nM monensin in the extracellular medium, the rate of labeling of GT1b diminished markedly to 20% of control; GD1a, GD1b, and GD2, to 35%; GQ1B to 48%; GD3 to 60%. Vigorous incorporation of label into GM3 was entirely undiminished by monensin. From these findings, it is suggested that ganglioside biosynthesis is compartmentalized in the cytodifferentiating embryonic neuron, with GM3 entirely, and GD3 and GQ1b partially, an extra-Golgi product. Extensive loss of neurites that occurred after several hours of exposure of the neurons to monensin could not be correlated directly with decreased ganglioside anabolism.
Hogan
M V
MV
Division of Molecular Biology and Neural Regeneration, Nathan S. Kline Institute for Psychiatric Research, New York State Office of Mental Health, Orangeburg 10962.
Saito
M
M
Rosenberg
A
A
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D005690:Galactose / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D008985:Monensin / Q000494:pharmacology*; D013687:Telencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D005732:Gangliosides; D008985:Monensin; D005690:Galactose