The localization of acid hydrolases was examined in Chinese hamster ovary cells with defective mannose 6-phosphate receptors; these mutants had been shown to exhibit reduced uptake and altered binding of exogenously added acid hydrolase (Robbins, A. R., Myerowitz, R., Youle, R. J., Murray, G. J., and Neville, D. M., Jr. (1981) J. Biol. Chem. 256, 10618-10622). Cells were grown in the presence o...

The composition and functions of the secreted proteome are controlled by the life spans of different proteins. However, unlike intracellular protein fate, intrinsic factors determining secreted protein aging and turnover have not been identified and characterized. Almost all secreted proteins are posttranslationally modified with the covalent attachment of N-glycans. We have discovered an intri...

Tay-Sachs disease (TSD), an autosomal recessive neurodegenerative condition, is the result of a deficiency of beta-hexosaminidase A (hex A). Heterozygotic individuals are screened by analysis for hex A and hex B activities; the percent of hex A is the critical determinant of carrier vs noncarrier status. Most laboratories use a heat-inactivation assay that exploits the differential thermolabili...

The GM2 gangliosidosis are a group of metabolic disorders in which deficiency of a lysosomal enzyme, hexosaminidase A (Hex A), leads to an abnormal intracellular accumulation of lipids in neurons and glia. Total deficiency is responsible for a fatal infantile disorder, Tay-Sachs disease, characterized by involution in motor abilities, hypotonia, seizures and cortical blindness, with death aroun...

Cell cultures were derived from the cerebra of a control and a Gm2 gangliosidosis (Tay-Sachs disease (TSD)) foetus. Both cell lines were identified as astrocytic, based on the ultrastructural demonstration of glial fibres. The control culture exhibited morphological differentiation when exposed to dibutyryl cAMP, a finding which was not observed with the TSD cells. The TSD culture demonstrated ...