The Interaction Between UPAR and Vitronectin Triggers Ligand-independent Adhesion Signalling by Integrins

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2014 Aug 30

PMID 25168639

Citations 44

Authors

Gian Maria Sarra Ferraris

Carsten Schulte

Valentina Buttiglione

Valentina De Lorenzi

Andrea Piontini

Massimiliano Galluzzi

Alessandro Podesta

Chris D Madsen

Nicolai Sidenius

Affiliations

Soon will be listed here.

Abstract

The urokinase-type plasminogen activator receptor (uPAR) is a non-integrin vitronectin (VN) cell adhesion receptor linked to the plasma membrane by a glycolipid anchor. Through structure-function analyses of uPAR, VN and integrins, we document that uPAR-mediated cell adhesion to VN triggers a novel type of integrin signalling that is independent of integrin-matrix engagement. The signalling is fully active on VN mutants deficient in integrin binding site and is also efficiently transduced by integrins deficient in ligand binding. Although integrin ligation is dispensable, signalling is crucially dependent upon an active conformation of the integrin and its association with intracellular adaptors such as talin. This non-canonical integrin signalling is not restricted to uPAR as it poses no structural constraints to the receptor mediating cell attachment. In contrast to canonical integrin signalling, where integrins form direct mechanical links between the ECM and the cytoskeleton, the molecular mechanism enabling the crosstalk between non-integrin adhesion receptors and integrins is dependent upon membrane tension. This suggests that for this type of signalling, the membrane represents a critical component of the molecular clutch.

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