A recognition marker required for uptake of a lysosomal enzyme by cultured fibroblasts

Structure of Nine Sialyl-Oligosaccharides Accumulated in Urine of Eleven Patients with Three Different Types of Sialidosis. Mucolipidosis II and Two New Types of Mucolipidosis

“…The specific role of sialidases and sialic acid in the biochemistry of glycoproteins may explain some of the recent observations described in literature. The electrophoretic changes in excreted N-acetylhexosaminidases in I-Cell disease [15], as well the non-uptake of abnormal lysosomal enzymes excreted from I-Cell fibroblasts [16,17] by normal fibroblasts suggest that in I-Cell disease a defect in the control of exocytosis resulting in abnormal enzyme excretion is probably the direct consequence of sialidase deficiency, in regard to Ashwell's theory [I 81. However many points remain obscure.…”

Mechanisms for the incorporation of proteins in membranes and organelles.

“…It was first found by Neufeld and her associates (90,191) that strains of genetically deficient fibroblasts (I cells) from patients with mucolipidosis II secrete lysosomal hydrolases into the medium rather than incorporating them into lysosomes . These enzymes, although enzymatically active, were found to lack a recognition marker for uptake by normal fibroblasts, whereas lysosomal hydrolases from normal cells could be taken up by a specific and saturatable process by both normal and I cell fibroblasts .…”

Discovery of the cellular and molecular basis of cholesterol control

“…Crucially, they showed that lysosomal enzymes secreted by I-cell fibroblasts fail to be recaptured by normal or I-cell fibroblasts, whereas the corresponding enzymes secreted by normal cells are taken up by I-cells. Neufeld and colleagues speculated on the existence of a cell surface receptor responsible for the recognition and internalization of lysosomal precursor proteins and that I-cell disease must affect some covalent feature of the lysosomal enzyme required for interaction with the receptor (9). Subsequent work by Sly and Kornfeld and colleagues revealed the nature of the mannose-6-phosphate (M6P) tag on a lysosomal precursor protein glycan, the M6P receptor responsible for precursor protein internalization in intracellular traffic and the I-cell gene, which encodes a Golgi membrane enzyme that tags lysosomal glycoprotein precursors en route to the lysosome (10,11).…”