Proteases and glycosidases on the surface of exosomes: Newly discovered mechanisms for extracellular remodeling

Emergence of the field of exosome biology has opened an exciting door to better understand communication between cells. These tiny nanovesicles act as potent regulators of biological function by delivering proteins, lipids and nucleic acids from the cell of origin to target cells. Recently, several enzymes including membrane-type 1 matrix metalloproteinase (MT1-MMP), insulin-degrading enzyme (IDE), sialidase and heparanase, among others, were localized on the surface of exosomes secreted by various cell types. These exosomal surface enzymes retain their activity and can degrade their natural substrates present within extracellular spaces. To date, enzymes on exosome surfaces have been associated with the mobilization of growth factors, degradation of extracellular matrix macromolecules and destruction of amyloid β plaques. This review focuses on the emerging role of exosomal surface enzymes and how this mechanism of remodeling within the extracellular space may regulate disease progression as related to cancer, inflammation and Alzheimer's disease. •Exosomes regulate cell communication by transferring proteins, lipids and nucleic acids between cells•New evidence demonstrates that enzymatically active proteases and glycosidases are present on the surface of some exosomes•These enzymes on exosome surfaces can degrade the ECM, liberate growth factors and alter cell adhesion and invasion•Enzymatic functions of exosomes have implications in the progression of cancer, inflammation and Alzheimer’s disease