Abstract
In human leucocytes, egress and counter-transport studies have shown that cystine transport across lysoscmal membranes is a saturable, stereospecific, and bidirectional process which is defective in cystinosis. MgCl2/MgATP (each 2mM) shifted the pH optimum for cystine counter-transport from pH 6.5 to pH 5.5, where a 2-fold stimulation of cystine transport was observed. This was caused by Mg++, not ATP, and was dose-dependent with a maximum at 4mM MgCl2. Stimulation was prevented by EDTA or NaATP. MgSO4 or MnCl2 could replace MgCl2. In other experiments, 35S-cystine clearance from normal, cystinotic, and I-cell (Mucolipidosis II) fibroblasts was measured. Cells were loaded to roughly equivalent levels of 35S-cystine, washed free of label, and harvested after 0, 30, 60, and 120 min at 37°C. 35S-Cystine (nmol/mg protein) was measured and half-times for cystine clearance calculated. For 2 normal strains, mean t½ was 38 min; cystinotic mean t½ was 734 min; I-cell mean t½ was over 800 min. I-Cells lack the enzyme responsible for formation of mannose-6-phosphate residues required for lysosomal enzyme recognition and uptake. From the cystine storage and impaired cystine clearance in I-cells, one may speculate that the cystine carrier requires a mannose-6-phosphate recognition marker, or that it may require processing by lysoscmal hydrolases which are deficient in I-cell fibroblasts.
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Gahl, W., Tietze, F., Butler, J. et al. LYSOSOMAL CYSTINE TRANSPORT: MG++EFFECTS AND I-CELL FIBROBLAST DEFECTS. Pediatr Res 18 (Suppl 4), 221 (1984). https://doi.org/10.1203/00006450-198404001-00768
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DOI: https://doi.org/10.1203/00006450-198404001-00768