TITLE:
The cellular microenvironment modulates the role of PAI-1 and vitronectin in mediating cell-matrix interactions
AUTHORS:
Sumit Goswami, Lawrence C. Thompson, Lindsay Wickman, Cynthia B. Peterson
KEYWORDS:
PAI-1; Vitronectin; Extracellular Matrix; Receptors
JOURNAL NAME:
Advances in Biological Chemistry,
Vol.3 No.1,
February
26,
2013
ABSTRACT: Plasminogen activator inhibitor-1 (PAI-1), a member
of the serine protease inhibitor (serpin) superfamily of proteins, circulates
in a complex with vitronectin. Furthermore, these two proteins are co-localized
in the extracellular matrix (ECM) in many different pathophysiological conditions.
Though PAI-1 is a well-characterized inhibitor of serine proteases, recent
emphasis has also focused on its protease-independent functions. Vitronectin,
a multi-domain protein that binds a wide variety of ligands and proteins,
exists in the circulation in a preferred monomeric state, while in the
extracellular matrix it exists as a multimer resulting from an altered
conformation. Though the mechanism for the conformational alterations and
compartmentalization in tissues is unknown, there are a number of
biomolecules including PAI-1 that appear to cause such changes. Experimental
analysis has established that PAI-1 induces association of vitronectin to
higher-order species in a concentration-dependent fashion [1]. This report extends
our investigations into the mechanism of the interaction between vitronectin
and PAI-1 to explore the physiological relevance of these higher-order
complexes for cellular adhesion and migration. In this study, we evaluate the
effects of the pericellular microenvironment on the functions of the multimeric
complexes in a variety of relevant biological settings. Our findings underscore
the importance of the variability of components within this microenvironment,
including different receptors and ECM components, in governing the way in which
the vitronectin/PAI-1 complex mediates cell-matrix interactions.