A functional interaction between liprin-alpha1 and B56gamma regulatory subunit of protein phosphatase 2A supports tumor cell motility

Published: 28 September 2022| Version 1 | DOI: 10.17632/wvt7kgsjvx.1
Contributors:
, Marta Ripamonti, Andrea Lamarca

Description

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.

Institutions

Ospedale San Raffaele, Universita Vita Salute San Raffaele

Categories

Cell Biology

Funding

Fondazione AIRC per la ricerca sul cancro

IG 2017 Id.20203

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