Palmitoyl-protein thioesterase deficiency in fibroblasts of individuals with infantile neuronal ceroid lipofuscinosis and I-cell disease

Linda A. Verkruyse, Marvin R. Natowicz, Sandra L. Hofmann

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Mutations in the gene encoding a recently described lysosomal enzyme, palmitoyl-protein thioesterase (PPT), have recently been shown to result in the neurodegenerative disorder, infantile neuronal ceroid lipofuscinosis (INCL). Reduced palmitoyl-protein thioesterase enzyme has been demonstrated previously in INCL brain and immortalized lymphoblasts. In the current paper, we demonstrate that: (1) PPT can be detected by immunoblotting and enzyme activity assays in normal human skin fibroblasts; (2) INCL fibroblasts are deficient in PPT activity; (3) I-cell disease fibroblasts show markedly reduced intracellular levels of PPT but markedly increased levels of PPT in cell culture medium. These data establish that PPT is transported to lysosomes via the lysosomal enzyme:lysosomal enzyme receptor phosphomannosyl recognition system under normal physiological conditions and provide the basis for a useful clinical assay for INCL.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1361
Issue number1
DOIs
StatePublished - Jul 10 1997

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Mucolipidoses
Neuronal Ceroid-Lipofuscinoses
Protein Deficiency
Fibroblasts
Enzymes
Enzyme Assays
Lysosomes
Ceroid lipofuscinosis, neuronal 1, infantile
palmitoyl-protein thioesterase
Immunoblotting
Neurodegenerative Diseases
Culture Media
Cell Culture Techniques
Skin
Mutation
Brain

Keywords

  • Fibroblast
  • I-cell disease
  • Infantile neuronal ceroid lipofuscinosis
  • Lysosomal starage disorder

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

Cite this

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title = "Palmitoyl-protein thioesterase deficiency in fibroblasts of individuals with infantile neuronal ceroid lipofuscinosis and I-cell disease",
abstract = "Mutations in the gene encoding a recently described lysosomal enzyme, palmitoyl-protein thioesterase (PPT), have recently been shown to result in the neurodegenerative disorder, infantile neuronal ceroid lipofuscinosis (INCL). Reduced palmitoyl-protein thioesterase enzyme has been demonstrated previously in INCL brain and immortalized lymphoblasts. In the current paper, we demonstrate that: (1) PPT can be detected by immunoblotting and enzyme activity assays in normal human skin fibroblasts; (2) INCL fibroblasts are deficient in PPT activity; (3) I-cell disease fibroblasts show markedly reduced intracellular levels of PPT but markedly increased levels of PPT in cell culture medium. These data establish that PPT is transported to lysosomes via the lysosomal enzyme:lysosomal enzyme receptor phosphomannosyl recognition system under normal physiological conditions and provide the basis for a useful clinical assay for INCL.",
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AU - Verkruyse, Linda A.

AU - Natowicz, Marvin R.

AU - Hofmann, Sandra L.

PY - 1997/7/10

Y1 - 1997/7/10

N2 - Mutations in the gene encoding a recently described lysosomal enzyme, palmitoyl-protein thioesterase (PPT), have recently been shown to result in the neurodegenerative disorder, infantile neuronal ceroid lipofuscinosis (INCL). Reduced palmitoyl-protein thioesterase enzyme has been demonstrated previously in INCL brain and immortalized lymphoblasts. In the current paper, we demonstrate that: (1) PPT can be detected by immunoblotting and enzyme activity assays in normal human skin fibroblasts; (2) INCL fibroblasts are deficient in PPT activity; (3) I-cell disease fibroblasts show markedly reduced intracellular levels of PPT but markedly increased levels of PPT in cell culture medium. These data establish that PPT is transported to lysosomes via the lysosomal enzyme:lysosomal enzyme receptor phosphomannosyl recognition system under normal physiological conditions and provide the basis for a useful clinical assay for INCL.

AB - Mutations in the gene encoding a recently described lysosomal enzyme, palmitoyl-protein thioesterase (PPT), have recently been shown to result in the neurodegenerative disorder, infantile neuronal ceroid lipofuscinosis (INCL). Reduced palmitoyl-protein thioesterase enzyme has been demonstrated previously in INCL brain and immortalized lymphoblasts. In the current paper, we demonstrate that: (1) PPT can be detected by immunoblotting and enzyme activity assays in normal human skin fibroblasts; (2) INCL fibroblasts are deficient in PPT activity; (3) I-cell disease fibroblasts show markedly reduced intracellular levels of PPT but markedly increased levels of PPT in cell culture medium. These data establish that PPT is transported to lysosomes via the lysosomal enzyme:lysosomal enzyme receptor phosphomannosyl recognition system under normal physiological conditions and provide the basis for a useful clinical assay for INCL.

KW - Fibroblast

KW - I-cell disease

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KW - Lysosomal starage disorder

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