SUMO-1 Sumo-1 Marks Lysosomes in Neurodegenerative Diseases and in Animal and Cellular Disease Models

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Author(s)
Wong, M.
Noe, N.
Meedeniya, Adrian
Richter-Landsberg, C.
Pountney, Dean
Year published
2010
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visible protein aggregates, or inclusion bodies, within neural cells. The ubiquitin homologue, SUMO-1, has been identified in sub-domains of pathological inclusion bodies in several neurodegenerative diseases. Inclusion bodies are believed to be formed actively in a defensive response to soluble cytotoxic protein aggregates. We hypothesised that SUMO-1 may become associated with lysosomes in this response. Protein aggregation was induced in 1321N1 glioma cells by proteasome inhibition with MG132 or by transient transfection with Q74-EGFP. Fluorescence immunohistochemistry identified co-localisation of SUMO-1 and the lysosomal ...
View more >visible protein aggregates, or inclusion bodies, within neural cells. The ubiquitin homologue, SUMO-1, has been identified in sub-domains of pathological inclusion bodies in several neurodegenerative diseases. Inclusion bodies are believed to be formed actively in a defensive response to soluble cytotoxic protein aggregates. We hypothesised that SUMO-1 may become associated with lysosomes in this response. Protein aggregation was induced in 1321N1 glioma cells by proteasome inhibition with MG132 or by transient transfection with Q74-EGFP. Fluorescence immunohistochemistry identified co-localisation of SUMO-1 and the lysosomal marker, cathepsin D, in both the transfected cells and MG132-treated cells, increasing over time at 24-96 hrs post-transfection/treatment. SUMO-1-positive lysosomes were also detected following MG132-treatment of 1321N1 cells expressing SUMO-1-GFP and stained with Lysotracker dye. SUMO-1 did not mark lysosomes in untransfected or sham treated cells. To determine if SUMO-1 also marks lysosomes in disease, we examined 5 cases of progressive supranuclear palsy (PSP), 5 cases of multiple system atrophy (MSA) and a rat Parkinson's disease model. Punctate co-localisation of cathepsin D and SUMO-1 was consistently associated with both the tau-positive PSP inclusions and the a-synuclein-positive MSA and rat PD model inclusions. A similar pattern was also found with the OLN-t40 oligodendrocyte model. These findings suggest a role for SUMO-1 in the autophagy-lysosome pathway linked to the response to protein aggregates.
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View more >visible protein aggregates, or inclusion bodies, within neural cells. The ubiquitin homologue, SUMO-1, has been identified in sub-domains of pathological inclusion bodies in several neurodegenerative diseases. Inclusion bodies are believed to be formed actively in a defensive response to soluble cytotoxic protein aggregates. We hypothesised that SUMO-1 may become associated with lysosomes in this response. Protein aggregation was induced in 1321N1 glioma cells by proteasome inhibition with MG132 or by transient transfection with Q74-EGFP. Fluorescence immunohistochemistry identified co-localisation of SUMO-1 and the lysosomal marker, cathepsin D, in both the transfected cells and MG132-treated cells, increasing over time at 24-96 hrs post-transfection/treatment. SUMO-1-positive lysosomes were also detected following MG132-treatment of 1321N1 cells expressing SUMO-1-GFP and stained with Lysotracker dye. SUMO-1 did not mark lysosomes in untransfected or sham treated cells. To determine if SUMO-1 also marks lysosomes in disease, we examined 5 cases of progressive supranuclear palsy (PSP), 5 cases of multiple system atrophy (MSA) and a rat Parkinson's disease model. Punctate co-localisation of cathepsin D and SUMO-1 was consistently associated with both the tau-positive PSP inclusions and the a-synuclein-positive MSA and rat PD model inclusions. A similar pattern was also found with the OLN-t40 oligodendrocyte model. These findings suggest a role for SUMO-1 in the autophagy-lysosome pathway linked to the response to protein aggregates.
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Conference Title
Posters OzBio2010 Combined Conference
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Copyright Statement
© The Author(s) 2010. The attached file is reproduced here in accordance with the copyright policy of the publisher. For information about this Conference please refer to the Conference website or contact the authors.
Subject
Cellular Nervous System