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University of Toronto

1. Lu, Lily. Elucidating the Regulation of ADAM17 Mediated Shedding of CX3CL1 from Vascular Endothelial Cells.

Degree: 2017, University of Toronto

CX3CL1 is an inducible chemokine that functions either as a transmembrane adhesion molecule, or when cleaved, as a soluble chemoattractant for leukocytes. Exposure to inflammatory mediators induces extensive proteolysis of CX3CL1 by the transmembrane protease ADAM17 in endothelial cells. The mechanisms governing this shedding remain undefined. Using single particle tracking, we found that CX3CL1 and ADAM17 were segregated at the plasma membrane. After stimulation with ADAM17 activator, PMA, CX3CL1 mobility remained unchanged while a small amount of ADAM17 was released from confinement. A modest increase in freely diffusing ADAM17 was observed after disruption of the actin cytoskeleton. Our data suggest that PMA has a modest effect on ADAM17 mobility and that the remodeling of actin cytoskeleton is unlikely to be the main mechanism of ADAM17-mediated proteolysis of CX3CL1. Even though β1 integrin activation has been suggested to regulate ADAM17 activity, our data suggests that it is insufficient for PMA-induced CX3CL1 shedding.

M.Sc.

Advisors/Committee Members: Robinson, Lisa, Medical Science.

Subjects/Keywords: ADAM17; CX3CL1; Endothelial Cells; Single Particle Tracking; Vascular Inflammation; 0379

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Lu, L. (2017). Elucidating the Regulation of ADAM17 Mediated Shedding of CX3CL1 from Vascular Endothelial Cells. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/79370

Chicago Manual of Style (16th Edition):

Lu, Lily. “Elucidating the Regulation of ADAM17 Mediated Shedding of CX3CL1 from Vascular Endothelial Cells.” 2017. Masters Thesis, University of Toronto. Accessed November 19, 2017. http://hdl.handle.net/1807/79370.

MLA Handbook (7th Edition):

Lu, Lily. “Elucidating the Regulation of ADAM17 Mediated Shedding of CX3CL1 from Vascular Endothelial Cells.” 2017. Web. 19 Nov 2017.

Vancouver:

Lu L. Elucidating the Regulation of ADAM17 Mediated Shedding of CX3CL1 from Vascular Endothelial Cells. [Internet] [Masters thesis]. University of Toronto; 2017. [cited 2017 Nov 19]. Available from: http://hdl.handle.net/1807/79370.

Council of Science Editors:

Lu L. Elucidating the Regulation of ADAM17 Mediated Shedding of CX3CL1 from Vascular Endothelial Cells. [Masters Thesis]. University of Toronto; 2017. Available from: http://hdl.handle.net/1807/79370

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