dc.contributor.author | Ripamonti, M | |
dc.contributor.author | Lamarca, A | |
dc.contributor.author | Davey, NE | |
dc.contributor.author | Tonoli, D | |
dc.contributor.author | Surini, S | |
dc.contributor.author | de Curtis, I | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-12-22T12:03:27Z | |
dc.date.available | 2022-12-22T12:03:27Z | |
dc.date.issued | 2022-09-28 | |
dc.identifier | ARTN 1025 | |
dc.identifier | 10.1038/s42003-022-03989-3 | |
dc.identifier.citation | Communications Biology, 2022, 5 (1), pp. 1025 - | en_US |
dc.identifier.issn | 2399-3642 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5612 | |
dc.identifier.eissn | 2399-3642 | |
dc.identifier.eissn | 2399-3642 | |
dc.identifier.doi | 10.1038/s42003-022-03989-3 | |
dc.description.abstract | Scaffold liprin-α1 is required to assemble dynamic plasma membrane-associated platforms (PMAPs) at the front of migrating breast cancer cells, to promote protrusion and invasion. We show that the N-terminal region of liprin-α1 contains an LxxIxE motif interacting with B56 regulatory subunits of serine/threonine protein phosphatase 2A (PP2A). The specific interaction of B56γ with liprin-α1 requires an intact motif, since two point mutations strongly reduce the interaction. B56γ mediates the interaction of liprin-α1 with the heterotrimeric PP2A holoenzyme. Most B56γ protein is recovered in the cytosolic fraction of invasive MDA-MB-231 breast cancer cells, where B56γ is complexed with liprin-α1. While mutation of the short linear motif (SLiM) does not affect localization of liprin-α1 to PMAPs, localization of B56γ at these sites specifically requires liprin-α1. Silencing of B56γ or liprin-α1 inhibits to similar extent cell spreading on extracellular matrix, invasion, motility and lamellipodia dynamics in migrating MDA-MB-231 cells, suggesting that B56γ/PP2A is a novel component of the PMAPs machinery regulating tumor cell motility. In this direction, inhibition of cell spreading by silencing liprin-α1 is not rescued by expression of B56γ binding-defective liprin-α1 mutant. We propose that liprin-α1-mediated recruitment of PP2A via B56γ regulates cell motility by controlling protrusion in migrating MDA-MB-231 cells. | |
dc.format | Electronic | |
dc.format.extent | 1025 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | NATURE PORTFOLIO | en_US |
dc.relation.ispartof | Communications Biology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Breast Neoplasms | |
dc.subject | Cell Movement | |
dc.subject | Female | |
dc.subject | Holoenzymes | |
dc.subject | Humans | |
dc.subject | Protein Phosphatase 2 | |
dc.subject | Serine | |
dc.subject | Threonine | |
dc.title | A functional interaction between liprin-α1 and B56γ regulatory subunit of protein phosphatase 2A supports tumor cell motility. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-09-13 | |
dc.date.updated | 2022-12-22T12:02:43Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1038/s42003-022-03989-3 | en_US |
rioxxterms.licenseref.startdate | 2022-09-28 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36171301 | |
pubs.issue | 1 | |
pubs.organisational-group | /ICR | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1038/s42003-022-03989-3 | |
pubs.volume | 5 | |
icr.researchteam | Short Linear Motif | en_US |
dc.contributor.icrauthor | Davey, Norman | |
icr.provenance | Deposited by Mr Arek Surman on 2022-12-22. Deposit type is initial. No. of files: 1. Files: A functional interaction between liprin-α1 and B56γ regulatory subunit of protein phosphatase 2A supports tumor cell motilit.pdf | |