A functional interaction between liprin-alpha1 and B56gamma regulatory subunit of protein phosphatase 2A supports tumor cell motility
PLEASE REFER TO THE PUBLICATION: Journal: Communications Biology. DOI : 10.1038/s42003-022-03989-3 Title : A functional interaction between liprin-α1 and B56γ regulatory subunit of protein phosphatase 2A supports tumor cell motility. Scaffold liprin-alpha1 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-alpha1 contains an LxxIxE motif interacting with B56 regulatory subunits of serine/threonine protein phosphatase 2A (PP2A). The specific interaction of B56gamma with liprin-alpha1 requires an intact motif, since two point mutations strongly reduce the interaction. B56gamma mediates the interaction of liprin-alpha1 with the heterotrimeric PP2A holoenzyme. Most B56gamma protein is recovered in the cytosolic fraction of invasive MDA-MB-231 breast cancer cells, where B56gamma is complexed with liprin-alpha1. While mutation of the short linear motif (SLiM) does not affect localization of liprin-alpha1 to PMAPs, localization of B56gamma at these sites specifically requires liprin-alpha1. Silencing of B56gamma or liprin-alpha1 inhibits to similar extent cell spreading on extracellular matrix, invasion, motility and lamellipodia dynamics in migrating MDA-MB-231 cells, suggesting that B56gamma-PP2A is a novel component of the PMAPs machinery regulating tumor cell motility. In this direction, inhibition of cell spreading by silencing liprin-alpha1 is not rescued by expression of B56gamma binding-defective liprin-alpha1 mutant. We propose that liprin-alpha1-mediated recruitment of PP2A via B56gamma regulates cell motility by controlling protrusion in migrating MDA-MB-231 cells.
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Refer to the published paper entitled: A functional interaction between liprin-alpha1 and B56gamma regulatory subunit of protein phosphatase 2A supports tumor cell motility.
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IG 2017 Id.20203