TY - JOUR
T1 - A hypothesis for I-cell disease
T2 - Defective hydrolases that do not enter lysosomes
AU - Hickman, Scot
AU - Neufeld, Elizabeth F.
PY - 1972/11/15
Y1 - 1972/11/15
N2 - Skin fibroblasts cultured from patients with I-cell disease ("I-cells") are markedly deficient in several lysosomal hydrolases, though these enzymes are found in surrounding medium. This situation is not brought about by increased lysosomal leakage, since I-cells were found as retentive of ingested enzymes (β-glucuronidase and α-L-iduronidase) as cells of other genotypes. On the other hand, hydrolases from I-cell medium were found only one-fifth to one-tenth as effective as their normal counterparts in experiments that involve uptake of the enzymes from the medium: correction of Hurler cells by α-L-iduronidase, correction of β-glucuronidase deficient cells by β-glucuronidase, and direct measurement of uptake of N-acetyl β-glucosaminidase by fibroblasts deficient in that enzyme. We suggest that the packaging of lysosomal enzymes requires their secretion followed by specific recognition and uptake. The I-cell mutation would interfere with this process by altering the recognition site on the hydrolases.
AB - Skin fibroblasts cultured from patients with I-cell disease ("I-cells") are markedly deficient in several lysosomal hydrolases, though these enzymes are found in surrounding medium. This situation is not brought about by increased lysosomal leakage, since I-cells were found as retentive of ingested enzymes (β-glucuronidase and α-L-iduronidase) as cells of other genotypes. On the other hand, hydrolases from I-cell medium were found only one-fifth to one-tenth as effective as their normal counterparts in experiments that involve uptake of the enzymes from the medium: correction of Hurler cells by α-L-iduronidase, correction of β-glucuronidase deficient cells by β-glucuronidase, and direct measurement of uptake of N-acetyl β-glucosaminidase by fibroblasts deficient in that enzyme. We suggest that the packaging of lysosomal enzymes requires their secretion followed by specific recognition and uptake. The I-cell mutation would interfere with this process by altering the recognition site on the hydrolases.
UR - http://www.scopus.com/inward/record.url?scp=0015511150&partnerID=8YFLogxK
U2 - 10.1016/0006-291X(72)90310-5
DO - 10.1016/0006-291X(72)90310-5
M3 - Article
C2 - 4345092
AN - SCOPUS:0015511150
VL - 49
SP - 992
EP - 999
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -