Levels of the Mahogunin Ring Finger 1 E3 ubiquitin ligase do not influence prion disease.

Abstract

Prion diseases are rare but invariably fatal neurodegenerative disorders. They are associated with spongiform encephalopathy, a histopathology characterized by the presence of large, membrane-bound vacuolar structures in the neuropil of the brain. While the primary cause is recognized as conversion of the normal form of prion protein (PrP(C)) to a conformationally distinct, pathogenic form (PrP(Sc)), the cellular pathways and mechanisms that lead to spongiform change, neuronal dysfunction and death are not known. Mice lacking the Mahogunin Ring Finger 1 (MGRN1) E3 ubiquitin ligase develop spongiform encephalopathy by 9 months of age but do not become ill. In cell culture, PrP aberrantly present in the cytosol was reported to interact with and sequester MGRN1. This caused endo-lysosomal trafficking defects similar to those observed when Mgrn1 expression is knocked down, implicating disrupted MGRN1-dependent trafficking in the pathogenesis of prion disease. As these defects were rescued by over-expression of MGRN1, we investigated whether reduced or elevated Mgrn1 expression influences the onset, progression or pathology of disease in mice inoculated with PrP(Sc). No differences were observed, indicating that disruption of MGRN1-dependent pathways does not play a significant role in the pathogenesis of transmissible spongiform encephalopathy.

• Authors: Derek Silvius, Rose Pitstick, Misol Ahn, Delisha Meishery, Abby Oehler, Gregory S Barsh, Stephen J DeArmond, George A Carlson, Teresa M Gunn
• Journal: PloS one (PLoS One) Vol. 8 Issue 1 Pg. e55575 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23383230 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Prions
• Mgrn1 protein, mouse
• Ubiquitin-Protein Ligases

Topics

• Animals
• Brain (metabolism, pathology)
• Disease Models, Animal
• Disease Progression
• Female
• Gene Expression
• Humans
• Mice
• Mice, Transgenic
• Prion Diseases (genetics, metabolism, mortality)
• Prions (metabolism)
• Ubiquitin-Protein Ligases (genetics, metabolism)