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Membrane-anchored proteases in endothelial cell biology

Antalis, Toni M.; Conway, Gregory D.; Peroutka, Raymond J.; Buzza, Marguerite S.

Current Opinion in Hematology: May 2016 - Volume 23 - Issue 3 - p 243–252
doi: 10.1097/MOH.0000000000000238
VASCULAR BIOLOGY: Edited by Edward F. Plow

Purpose of review The endothelial cell plasma membrane is a metabolically active, dynamic, and fluid microenvironment where pericellular proteolysis plays a critical role. Membrane-anchored proteases may be expressed by endothelial cells as well as mural cells and leukocytes with distribution both inside and outside of the vascular system. Here, we will review the recent advances in our understanding of the direct and indirect roles of membrane-anchored proteases in vascular biology and the possible conservation of their extravascular functions in endothelial cell biology.

Recent findings Membrane-anchored proteases belonging to the serine or metalloprotease families contain amino-terminal or carboxy-terminal domains, which serve to tether their extracellular protease domains directly at the plasma membrane. This architecture enables protease function and substrate repertoire to be regulated through dynamic localization in distinct areas of the cell membrane. These proteases are proving to be key components of the cell machinery for regulating vascular permeability, generation of vasoactive peptides, receptor tyrosine kinase transactivation, extracellular matrix proteolysis, and angiogenesis.

Summary A complex picture of the interdependence between membrane-anchored protease localization and function is emerging that may provide a mechanism for precise coordination of extracellular signals and intracellular responses through communication with the cytoskeleton and with cellular signaling molecules.

Center for Vascular and Inflammatory Diseases and the Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA

Correspondence to Toni M. Antalis, PhD, Department of Physiology and the Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, 800 West Baltimore Street, Baltimore, MD 21201, USA. Tel: +1 410 706 8222; fax: +1 410 706 8121; e-mail:

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