I-CELL DISEASE: IMPAIRED FIBROBLAST UPTAKE OF β-HEXOSAMINIDASE IS NOT DUE TO EXCESS SIALIC ACID

Abstract

Cultured skin fibroblasts from patients with I-cell disease (ICD; mucolipidosis II) are characterized by deficiency of lysosomal enzymes, including β-hexosaminidase (β-hex), which are greatly increased in culture fluid. Whereas normal fibroblast-excreted lysosomal enzymes are pinocytosed by ICD cells, ICD-excreted enzymes are not pinocytosed either by non-ICD cells or, presumably, by ICD cells. Our previous finding of excess sialic acid on ICD-excreted β-hex suggested that its presence may result in impaired enzyme uptake, perhaps by masking galactose residues necessary for recognition by a receptor analogous to that on hepatocyte plasma membrane. Desialylation of ICD-excreted β-hex with Cl. perfringens neuraminidase, however, did not enhance enzyme uptake by β-hex deficient, non-ICD cells. Similarly, β-hex from normal plasma was not taken up by these cells whether or not sialic acid had been removed. In contrast, β-hex from normal seminal fluid, also similar to ICD-excreted β-hex in net charge and neuraminidase sensitivity, was pinocytosed irrespective of sialic acid removal. Thus the presence of neuraminidase-susceptible sialic acid is not responsible for impaired β-hex uptake, and the recently reported neuraminidase deficiency in ICD fibroblasts (Thomas et.al., Biochem. Biophys. Res. Comm. 71: 188, 1976) may not be directly related to this phenomenon. Carbohydrate residues other than galactose may be involved in recognition and uptake of lysosomal enzymes by fibroblasts, which may be masked or absent in ICD-excreted β-hex.

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