Journal of Cell Science vol:129 issue:8 pages:1605-1618
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.