Abnormal expression of?-L-fucosidase in lymphoid cell lines of fucosidosis patients

Publisher Website
Google Scholar
Abstract
Fucosidosis is an autosomal recessive lysosomal storage disease due to a deficiency ofα-L-fucosidase activity in tissues and body fluids. Exponentially growing lymphoid cell cultures from four fucosidosis patients had 2.7-fold to 15.6-fold less extracellularα-L-fucosidase protein and 28.8-fold to 144.0-fold less intracellularα-L-fucosidase protein with negligible catalytic activity, compared to the mean of 19 control cultures. The percentage of totalα-L-fucosidase protein released extracellularly by cultures from the four patients was 64 to 85%, compared to 35±9% for control cultures. Intracellular and extracellular enzyme forms in fucosidosis and control cell lines were glycoproteins containing polypeptide chains ofMr=52,000. During a 1.5-hr pulse-label with35S-methionine,α-L-fucosidase was synthesized by control cells and two fucosidosis cell lines as an intracellular form withMr=58,000. During a subsequent 21-hr chase with unlabeled methionine, mutant enzyme was almost entirely processed to an extracellular form withMr=62,000. In contrast, only 25–30% of control enzyme was processed to an extracellular form (Mr=62,000), with the remainder retained intracellularly (Mr=60,000). In the other two fucosidosis cell lines,α-L-fucosidase was synthesized as an intracellular form withMr=56,000 that was processed to an extracellular form withMr=60,000. In summary, the fucosidosis mutation(s) affected the catalytic activity, quantity, and extracellular release ofα-L-fucosidase as expressed by lymphoid cells.