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  • The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration.

The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration.

EMBO reports (2018-05-26)
Samuel J Atkinson, Aleksander M Gontarczyk, Abdullah Aa Alghamdi, Tim S Ellison, Robert T Johnson, Wesley J Fowler, Benjamin M Kirkup, Bernardo C Silva, Bronwen E Harry, Jochen G Schneider, Katherine N Weilbaecher, Mette M Mogensen, Mark D Bass, Maddy Parsons, Dylan R Edwards, Stephen D Robinson
ABSTRACT

Integrin β3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3-dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3-integrin levels are reduced.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-Talin antibody produced in mouse, clone 8d4, ascites fluid
Sigma-Aldrich
Rac1 Activation Magnetic Beads Pulldown Assay, Non-radioactive Rac1 Activation Assay Kit can be used to precipitate Rac1-GTP from cell lysates, & detection by a Rac1 specific monoclonal antibody.