PP2A binds to the LIM domains of lipoma-preferred partner through its PR130/B ″subunit to regulate cell adhesion and migration

V Janssens, K Zwaenepoel, C Rossé… - Journal of cell …, 2016 - journals.biologists.com
V Janssens, K Zwaenepoel, C Rossé, MMR Petit, J Goris, PJ Parker
Journal of cell science, 2016journals.biologists.com
Here, we identify the LIM protein lipoma-preferred partner (LPP) as a binding partner of a
specific protein phosphatase 2A (PP2A) heterotrimer that is characterised by the regulatory
PR130/B ″α1 subunit (encoded by PPP2R3A). The PR130 subunit interacts with the LIM
domains of LPP through a conserved Zn2+-finger-like motif in the differentially spliced N-
terminus of PR130. Isolated LPP-associated PP2A complexes are catalytically active.
PR130 colocalises with LPP at multiple locations within cells, including focal contacts, but is …
Abstract
Here, we identify the LIM protein lipoma-preferred partner (LPP) as a binding partner of a specific protein phosphatase 2A (PP2A) heterotrimer that is characterised by the regulatory PR130/B″α1 subunit (encoded by PPP2R3A). The PR130 subunit interacts with the LIM domains of LPP through a conserved Zn2+-finger-like motif in the differentially spliced N-terminus of PR130. Isolated LPP-associated PP2A complexes are catalytically active. PR130 colocalises 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 domain of PR130 that binds to the PP2A catalytic subunit (PP2A/C), suggesting that PR130–LPP complex formation is dynamic and that permanent recruitment of PP2A activity might 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 to LPP. Our data highlight the importance of specific, locally recruited PP2A complexes in cell adhesion and migration dynamics.
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