Upregulation of the Endosomal-Lysosomal Pathway in the Trembler-J Neuropathy
| Autor: | Eric M. Shooter, Lucia Notterpek, G J Snipes |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Cytoplasm
Heterozygote Glycosylation Golgi Apparatus Endosomes Biology Endoplasmic Reticulum medicine.disease_cause Mice Mice Neurologic Mutants Myelin Downregulation and upregulation Western blot Antibody Specificity Mutant protein Peripheral myelin protein 22 medicine Animals Peripheral Nerves Mutation medicine.diagnostic_test General Neuroscience Homozygote Articles Trembler biology.organism_classification Molecular biology Up-Regulation Myelin basic protein Phenotype medicine.anatomical_structure biology.protein Schwann Cells Lysosomes Biomarkers Myelin Proteins Demyelinating Diseases |
| Zdroj: | The Journal of Neuroscience. 17:4190-4200 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.17-11-04190.1997 |
| Popis: | A nonconservative leucine to proline mutation in peripheral myelin protein 22 (PMP22) causes the Trembler-J (TrJ) neuropathy in mice and humans. The expression levels and localization of the PMP22 protein in theTrJmouse have not been previously determined. The aim of our studies was to reevaluate the extent of myelin deficit in genotyped heterozygous and homozygous animals and to examine how theTrJmutation alters the normalin vivopost-translational processing of PMP22. Morphological studies show evidence for primary dysmyelination and myelin instability in affected animals. As expected, Western blot analysis indicates that in adult heterozygousTrJanimals, the level of PMP22 is markedly decreased, similar to myelin basic protein and protein zero, whereas myelin-associated glycoprotein is largely unaffected. The decrease in myelin protein expression is associated with an increase in lysosomal biogenesis, suggestive of augmented endocytosis or autophagy. Double-immunolabeling experiments show the accumulation of PMP22 in endosomal/lysosomal structures ofTrJSchwann cells, and chloroquine treatment of nerve segments indicates that the degradation of protein zero, PMP22, and myelin basic protein is augmented inTrJnerves. These studies suggest that theTrJmutation alters myelin stability and that the mutant protein is likely degraded via the lysosomal pathway. |
| Databáze: | OpenAIRE |
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