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.

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.
AuthorsSu Xu, David E Sleat, Michel Jadot, Peter Lobel
JournalThe Biochemical journal (Biochem J) Vol. 428 Issue 3 Pg. 355-62 (Jun 15 2010) ISSN: 1470-8728 [Electronic] England
PMID20370715 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Glial Fibrillary Acidic Protein
  • Serine Proteases
  • Aminopeptidases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • tripeptidyl-peptidase 1
  • Aminopeptidases (genetics, metabolism)
  • Animals
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (genetics, metabolism)
  • Glial Fibrillary Acidic Protein (genetics, metabolism)
  • Lysosomal Storage Diseases (genetics, metabolism)
  • Lysosomes (metabolism)
  • Mice
  • Microscopy, Confocal
  • Models, Animal
  • Neuronal Ceroid-Lipofuscinoses (genetics, metabolism)
  • Serine Proteases (genetics, metabolism)

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