TY - JOUR
T1 - Lysosomal targeting of palmitoyl-protein thioesterase
AU - Verkruyse, Linda A.
AU - Hofmann, Sandra L.
PY - 1996
Y1 - 1996
N2 - Palmitoyl-protein thioesterase is a newly described long chain fatty- acid hydrolase that removes fatty acyl groups from modified cysteines in proteins. We have recently identified palmitoyl-protein thioesterase as the defective enzyme in the recessive hereditary neurological degenerative disorder infantile neuronal ceroid lipofuscinosis (Vesa, J., Hellsten, E., Verkruyse, L. A., Camp, L. A., Rapola, J., Santavuori, P., Hofmann, S. L., and Peltonen, L. (1995) Nature 376, 584-587). A defect in a lysosomal enzyme had been postulated for the disease, but until recently, the relevant defective lysosomal enzyme had not been identified. In this paper, we present evidence for the lysosomal localization of palmitoyl-protein thioesterase. We show that COS cells take up exogenously supplied palmitoyl-protein thioesterase intracellularly and that the cellular uptake is blocked by mannose 6-phosphate, a hallmark of lysosomal enzyme trafficking. The enzyme contains endoglycosidase H-sensitive oligosaccharides that contain phosphate groups. Furthermore, palmitoyl-protein thioesterase cosediments with lysosomal enzyme markers by Percoll density gradient centrifugation. Interestingly, the pH optimum for the enzyme is in the neutral range, a property shared by two other lysosomal enzymes that remove post-translational protein modifications. These findings suggest that palmitoyl-protein thioesterase is a lysosomal enzyme and that infantile neuronal ceroid lipofuscinosis is properly classified as a lysosomal storage disorder.
AB - Palmitoyl-protein thioesterase is a newly described long chain fatty- acid hydrolase that removes fatty acyl groups from modified cysteines in proteins. We have recently identified palmitoyl-protein thioesterase as the defective enzyme in the recessive hereditary neurological degenerative disorder infantile neuronal ceroid lipofuscinosis (Vesa, J., Hellsten, E., Verkruyse, L. A., Camp, L. A., Rapola, J., Santavuori, P., Hofmann, S. L., and Peltonen, L. (1995) Nature 376, 584-587). A defect in a lysosomal enzyme had been postulated for the disease, but until recently, the relevant defective lysosomal enzyme had not been identified. In this paper, we present evidence for the lysosomal localization of palmitoyl-protein thioesterase. We show that COS cells take up exogenously supplied palmitoyl-protein thioesterase intracellularly and that the cellular uptake is blocked by mannose 6-phosphate, a hallmark of lysosomal enzyme trafficking. The enzyme contains endoglycosidase H-sensitive oligosaccharides that contain phosphate groups. Furthermore, palmitoyl-protein thioesterase cosediments with lysosomal enzyme markers by Percoll density gradient centrifugation. Interestingly, the pH optimum for the enzyme is in the neutral range, a property shared by two other lysosomal enzymes that remove post-translational protein modifications. These findings suggest that palmitoyl-protein thioesterase is a lysosomal enzyme and that infantile neuronal ceroid lipofuscinosis is properly classified as a lysosomal storage disorder.
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U2 - 10.1074/jbc.271.26.15831
DO - 10.1074/jbc.271.26.15831
M3 - Article
C2 - 8663305
AN - SCOPUS:0030009044
SN - 0021-9258
VL - 271
SP - 15831
EP - 15836
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 26
ER -