title: PP2A binds to the LIM domains of lipoma-preferred partner through its PR130/B″ subunit to regulate cell adhesion and migration.
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.
authors.affiliation: Francis Crick Institute, Protein Phosphorylation Laboratory, 44 Lincoln's Inn Fields, London WC2A 3PX, UK Laboratory of Protein Phosphorylation and Proteomics, Dept. of Cellular and Molecular Medicine, KU Leuven, Herestraat 49 PO-box 901, Leuven B-3000, Belgium veerle.janssens@med.kuleuven.be peter.parker@crick.ac.uk.
authors.forename: Veerle
authors.identifier: http://orcid.org/0000-0002-6772-8448
authors.initials: V
authors.lastname: Janssens
authors.affiliation: Laboratory of Protein Phosphorylation and Proteomics, Dept. of Cellular and Molecular Medicine, KU Leuven, Herestraat 49 PO-box 901, Leuven B-3000, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Zwaenepoel
authors.affiliation: Francis Crick Institute, Protein Phosphorylation Laboratory, 44 Lincoln's Inn Fields, London WC2A 3PX, UK Research Centre, Institut Curie, Paris 75005, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Rossé
authors.affiliation: Molecular Oncology Laboratory, Dept. of Human Genetics, KU Leuven, Herestraat 49 PO-box 602, Leuven B-3000, Belgium.
authors.forename: Marleen M R
authors.identifier: http://orcid.org/0000-0003-4557-0245
authors.initials: MM
authors.lastname: Petit
authors.affiliation: Laboratory of Protein Phosphorylation and Proteomics, Dept. of Cellular and Molecular Medicine, KU Leuven, Herestraat 49 PO-box 901, Leuven B-3000, Belgium.
authors.forename: Jozef
authors.initials: J
authors.lastname: Goris
authors.affiliation: Francis Crick Institute, Protein Phosphorylation Laboratory, 44 Lincoln's Inn Fields, London WC2A 3PX, UK Division of Cancer Studies King's College London, Guy's Hospital Campus, Thomas Street, London SE1 9RT, UK veerle.janssens@med.kuleuven.be peter.parker@crick.ac.uk.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Parker
mesh_terms: D020134:Catalytic Domain / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D022001:Focal Adhesions / Q000235:genetics; D006801:Humans; D060588:LIM Domain Proteins / Q000378:metabolism*; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; D060588:LIM Domain Proteins; C103594:LPP protein, human; D034741:RNA, Small Interfering; C525688:PPP2R3A protein, human; D054648:Protein Phosphatase 2
keywords: Cell adhesion; Cell migration; LIM domain; Lipoma-preferred partner; Protein phosphatase 2A; Zn2+-finger