Gangliosides of the plasma membrane are important modulators of cellul
ar functions, Previous work from our laboratory had suggested that a p
lasma membrane sialidase was involved in growth control and differenti
ation in cultured human neuroblastoma cells (SK-N-MC), but its substra
tes had remained obscure, We now performed sialidase specificity studi
es in subcellular fractions and found ganglioside GM3 desialylating ac
tivity in presence of Triton X-100 to be associated with the plasma me
mbrane, but absent in lysosomes, This Triton-activated plasma membrane
enzyme desialylated also gangliosides GD1a, GD1b, and GT1b, thereby f
orming GM1; cleavage of GM1 and GM2, however, was not observed, Sialid
ase activity towards the glycoprotein fetuin with modified C-7 sialic
acids and towards 4-methylumbelliferyl neuraminate was solely found in
lysosomal, but not in plasma membrane fractions, The role of the plas
ma membrane sialidase in ganglioside desialylation of living cells was
examined by following the fate of [H-3]galactose-labelled individual
gangliosides in pulse-chase experiments in absence and presence of the
extracellular sialidase inhibitor 2-deoxy-2,3-dehydro-N-acetylneurami
nic acid, When the plasma membrane sialidase was inhibited, radioactiv
ity of all gangliosides chased at the same rate, In the absence of inh
ibitor, GM3, GD1a, GD1b, GD2, GD3 and GT1b were degraded at a consider
ably faster rate in confluent cultures, whereas the GM1-pool seemed to
be filled by the desialylation of higher gangliosides. The results th
us suggest that the plasma membrane sialidase causes selective ganglio
side desialylation, and that such surface glycolipid modification trig
gers growth control and differentiation in human neuroblastoma cells.