A-disintegrin-and-metalloproteinase (ADAM) 10 activity on resting and activated platelets

Adam David Facey, Isaac Pinar, Jane Frances Arthur, Jian Lin Qiao, Jing Jing, Belden Mado, Josie Joy Carberry, Robert Keith Andrews, Elizabeth Ellen Gardiner

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14 Citations (Scopus)

Abstract

The primary platelet collagen receptor, glycoprotein VI (GPVI), plays an important role in platelet activation and thrombosis. The ectodomain of human GPVI (sGPVI) is proteolytically shed from human platelets by a-disintegrin-and-metalloproteinase 10 (ADAM10). In this study, we used a novel ADAM10-sensitive fluorescence resonance energy transfer sensor to analyze ADAM10-mediated shedding of GPVI from human platelets in response to the exposure of GPVI ligands collagen-related peptide (10 ?g/mL), collagen (10 ?g/mL), and convulxin (0.1 ?g/mL) to shear stress (1000-10000 s-1, 5 min), or a generic activator of metalloproteinases, N-ethylmaleimide (NEM, 5 mM). Elevated shear, NEM, or ligand engagement of GPVI all induced shedding of GPVI, as detected by release of sGPVI; however, only shear or NEM significantly increased ADAM10 enzyme activity. ADAM10 activity was also detectable on the surface of thrombi formed on a collagen-coated surface under flow conditions. Our findings indicate different mechanisms regulate shear- and ligand-induced shedding and shear forces found within the vasculature can regulate ADAM10 activity.
Original languageEnglish
Pages (from-to)1187 - 1194
Number of pages8
JournalBiochemistry
Volume55
Issue number8
DOIs
Publication statusPublished - 2016

Cite this

Facey, A. D., Pinar, I., Arthur, J. F., Qiao, J. L., Jing, J., Mado, B., ... Gardiner, E. E. (2016). A-disintegrin-and-metalloproteinase (ADAM) 10 activity on resting and activated platelets. Biochemistry, 55(8), 1187 - 1194. https://doi.org/10.1021/acs.biochem.5b01102