Regulation of ganglioside and sialoglycoprotein biosynthesis—Effect of drugs affecting membrane flow

Abstract

The labelling of gangliosides and sialoglycoproteins (SGP) after injecting intraocularly 30 ?Ci of [(3)H]ManNAc was studied in chickens that had previously received, also intraocularly, 30 or 70 nmol of monensin in 10 ?l of ethanol or 24 ?g of colchicine in 10 ?l saline. Controls received ethanol or saline only. Colchicine at doses that almost completely block the axonal transport to the optic tectum does not affect the labelling of those sialocompounds. The translocation of gangliosides and SGP, measured as a percentage of accessibility to the sialidase was inhibited by colchicine, but this effect was different for gangliosides and for SGP. In contrast, monensin, also at doses that block axonal transport, inhibits the synthesis and the translocation of gangliosides and SGP. It also modifies the labelling pattern of retinal gangliosides, which with respect to the normal pattern shows an increase in the relative labelling of GM(3), GD(3), GM(1) and probably GD(1b) and a decrease in GD(1a) and GT(1b). The activity of UDP-GalNAc: GM(3), GalNAc transferase (EC 2.4.1.79) of retina membranes of chickens that received an intraocular injection of monensin 4 h before being sacrificed showed a dose-dependent decrease with respect to the controls. In experiments in vitro monensin at a concentration of 3 mM failed to inhibit this activity.