Diversity, developmental regulation and distribution of murine PR55/B subunits of protein phosphatase 2A

Schmidt, Karsten, Kins, Stefan, Schild, Andreas, Nitsch, Roger M., Hemmings, Brian A. and Gotz, Juergen (2002) Diversity, developmental regulation and distribution of murine PR55/B subunits of protein phosphatase 2A. European Journal of Neuroscience, 16 11: 2039-2048. doi:10.1046/j.1460-9568.2002.02274.x


Author Schmidt, Karsten
Kins, Stefan
Schild, Andreas
Nitsch, Roger M.
Hemmings, Brian A.
Gotz, Juergen
Title Diversity, developmental regulation and distribution of murine PR55/B subunits of protein phosphatase 2A
Journal name European Journal of Neuroscience   Check publisher's open access policy
ISSN 0953-816X
1460-9568
Publication date 2002-12
Sub-type Article (original research)
DOI 10.1046/j.1460-9568.2002.02274.x
Open Access Status Not yet assessed
Volume 16
Issue 11
Start page 2039
End page 2048
Total pages 10
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Protein phosphatase (PP2A) 2A is a hetero-trimeric holoenzyme that consists of a core dimer composed of a catalytic subunit that is tightly complexed with the scaffolding subunit PR65/A. This core dimer associates with variable regulatory subunits of the PR55/B, PR61/B′, PR72/B″ and PR93/PR110/B‴ families. As PP2A holoenzymes containing PR55/B have been shown to be involved in the pathogenesis of Alzheimer's disease, we characterized the PR55/B family with particular emphasis on its distribution and expression in the brain. We determined the genomic organization of all members of the PR55/B family and cloned their murine cDNAs. Thereby, two novel splice variants of PR55/Bβ were identified. In addition, Northern blot analysis revealed multiple transcripts for the different PR55 subunits, suggesting a higher variability within the PR55 family. In situ hybridization analysis revealed that all PR55/B subunits were widely expressed in the brain. PR55/Bα and Bβ protein expression varies significantly in areas of the brain affected by neurodegenerative diseases such as the hippocampus or cerebellum. At the cellular level, PR55/Bβ protein expression was confined to neurons, whereas PR55/Bα was also expressed in activated astrocytes indicating that the PR55 isoforms confer a different function to the holoenzyme complex. As PP2A dysfunction has been demonstrated to contribute to various human diseases, dissecting the PP2A holoenzyme and its particular function in different cell types will assist in the development of novel therapeutic strategies.
Keyword Alzheimer's disease
Brain
Holoenzyme
Spinocerebellar ataxia
Splice variant
WD-40 repeat
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Ageing Dementia Research Publications
 
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