Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal neurodegenerative disease of children caused by mutations in TPP1, the gene encoding the lysosomal protease tripeptidyl peptidase 1. LINCL is characterized by lysosomal accumulation of storage material of which only a single protein component, subunit c of mitochondrial ATP synthase, has been well established to date. Identification of other protein constituents of the storage material could provide useful insights into the pathophysiology of disease and the natural substrates for TPP1. We have therefore initiated a proteomic analysis of storage material in brain from a LINCL mouse model. One protein, GFAP (glial fibrillary acidic protein), was found to be elevated in the LINCL mice compared with normal controls in both isolated storage bodies and a lysosome-enriched subcellular fraction that contains storage material. To determine whether GFAP accumulates within the lysosome in LINCL, we examined its intracellular distribution using subcellular fractionation and morphological methods. These experiments demonstrate that GFAP is not a component of the storage material in LINCL, suggesting that reports of GFAP storage in other NCLs may need to be re-examined. A number of other proteins were elevated in the storage material and/or lysosome-enriched fraction from the LINCL mice, but it remains unclear whether these proteins are true constituents of the storage material or, like GFAP, whether they associate with this material upon purification.
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Research Article|
May 27 2010
Glial fibrillary acidic protein is elevated in the lysosomal storage disease classical late-infantile neuronal ceroid lipofuscinosis, but is not a component of the storage material
Su Xu;
Su Xu
*Center for Advanced Biotechnology and Medicine and Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854, U.S.A.
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David E. Sleat;
David E. Sleat
*Center for Advanced Biotechnology and Medicine and Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854, U.S.A.
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Michel Jadot;
Michel Jadot
†Laboratoire de Chimie Physiologique, Unite de Recherche en Physiologie Moleculaire, Facultes Universitaires Notre-Dame de la Paix, 61 Rue de Bruxelles, 5000 Namur, Belgium
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Peter Lobel
Peter Lobel
1
*Center for Advanced Biotechnology and Medicine and Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854, U.S.A.
1To whom correspondence should be addressed (email lobel@cabm.rutgers.edu).
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Publisher: Portland Press Ltd
Received:
January 21 2010
Revision Received:
March 29 2010
Accepted:
April 06 2010
Accepted Manuscript online:
April 06 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 428 (3): 355–362.
Article history
Received:
January 21 2010
Revision Received:
March 29 2010
Accepted:
April 06 2010
Accepted Manuscript online:
April 06 2010
Citation
Su Xu, David E. Sleat, Michel Jadot, Peter Lobel; Glial fibrillary acidic protein is elevated in the lysosomal storage disease classical late-infantile neuronal ceroid lipofuscinosis, but is not a component of the storage material. Biochem J 15 June 2010; 428 (3): 355–362. doi: https://doi.org/10.1042/BJ20100128
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