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CSB Seminar: Exerting and sensing forces during integrin-mediated phagocytosis
April 9, 2021 @ 11:00 am - 12:00 pm
“Exerting and sensing forces during integrin-mediated phagocytosis”
Valentin Jaumouillé, Assistant Professor
Department of Molecular Biology and Biochemistry, Simon Fraser University
Abstract:
Professional phagocytes are innate immune cells specialized in the uptake and clearance of large particulate materials including infiltrated microbes, apoptotic cells and debris. αMβ2 integrins (also called complement receptor 3) are highly expressed in macrophages and neutrophils. These integrins are thought to be the main phagocytic receptors for many pathogens, and participate in the clearance of dead cells and cancer cells. However, internalization of these different targets involve various physical constraints that professional phagocytes must overcome, including cortical and membrane tensions. In other contexts, such as cell adhesion and migration, cells deform and move using surface-attached integrins, which are coupled to mechanical forces generated by the actin cytoskeleton. By analogy, we asked whether phagocytosis required mechanical coupling of αMβ2 integrins to the actin cytoskeleton. Using quantitative live cell imaging, we found that particle internalization was driven by formation of Arp2/3 and formin-dependent actin protrusions that wrapped around the particle. Focal complex-like adhesions formed in the phagocytic cup, which contained β2 integrins, focal adhesion proteins and tyrosine kinases. Perturbation of talin and syk demonstrated that a talin-dependent mechanical link between integrins, and actin and a syk-mediated recruitment of vinculin independently of myosin II, enabled force transmission to target particles and promoted phagocytosis. Altering target mechanical properties demonstrated more efficient phagocytosis of stiffer targets, which could enable the discrimination of different targets based on their mechanical properties. Thus, macrophages build a myosin II-independent mechanosensitive molecular clutch, which couples integrins to cytoskeletal forces to control particle engulfment.
Friday, April 9th, 2021 at 11:00am
https://utoronto.zoom.us/j/94049486250
Host: Sergey Plotnikov (sergey.plotnikov@utoronto.ca)