1. PP2A binds the LIM-domains of Lipoma Preferred Partner via its PR130/B' subunit to regulate cell adhesion and migration
- Author
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Karen Zwaenepoel, Marleen M.R. Petit, Veerle Janssens, Carine Rossé, Peter J. Parker, and Jozef Goris
- Subjects
0301 basic medicine ,Protein subunit ,Plasma protein binding ,Biology ,Bioinformatics ,Article ,Focal adhesion ,03 medical and health sciences ,Cell Movement ,Catalytic Domain ,Cell Line, Tumor ,Humans ,Protein Phosphatase 2 ,RNA, Small Interfering ,Cell adhesion ,LIM domain ,Focal Adhesions ,Cell migration ,Cell Biology ,Protein phosphatase 2 ,LIM Domain Proteins ,Fusion protein ,Cell biology ,body regions ,Cytoskeletal Proteins ,030104 developmental biology ,Protein Binding - Abstract
Here we identify the LIM protein Lipoma Preferred Partner (LPP) as a novel binding partner of a specific Protein Phosphatase 2A (PP2A) heterotrimer characterised by the regulatory PR130/B"α1 subunit. PR130 interacts with the LIM domains of LPP via a conserved zinc finger-like motif in its differentially spliced N-terminus. Isolated LPP-associated PP2A complexes are catalytically active. PR130 co-localises with LPP at multiple locations within cells, including focal contacts, but is specifically excluded from mature focal adhesions, where LPP is still present. An LPP-PR130 fusion protein only localises to focal adhesions upon deletion of the PR130 PP2A/C-binding domain, suggesting that PR130-LPP complex formation is dynamic, and permanent recruitment of PP2A activity may be unfavourable for focal adhesion maturation. Accordingly, siRNA-mediated knockdown of PR130 increases adhesion of HT1080 fibrosarcoma cells onto collagen I and decreases their migration in scratch wound and transwell assays. Complex formation with LPP is mandatory for these PR130-PP2A functions, as neither phenotype can be rescued by re-expression of a PR130 mutant that no longer binds LPP. Our data highlight the importance of specific, locally recruited PP2A complexes in cell adhesion/migration dynamics. ispartof: Journal of Cell Science vol:129 issue:8 pages:1605-1618 ispartof: location:England status: published
- Published
- 2016