CSB Seminar Series – Costin Antonescu, PhD – Toronto Metropolitan University

CSB Departmental Seminar

Costin Antonescu, PhD

Toronto Metropolitan University, Department of Chemistry and Biology

TITLE: Dynamic cell surface nanoscale organization controls receptor signaling in breast cancer cells

ABSTRACT: The epidermal growth factor receptor (EGFR) is a central regulator of cell physiology and upregulation of EGFR drives progression of many tumors, including in triple negative breast cancer. EGFR is activated by binding to ligands at the cell surface, in turn triggering receptor dimerization, activation of kinase activity and then subsequent engagement of numerous intracellular signaling intermediates. We use a range of microscopy methods to study the nanoscale organization and regulation of EGFR ligand binding and engagement of specific signaling pathways. Using single-particle tracking of EGFR, we resolve how specific protein-based membrane nanodomains gate the mobility of EGFR in the plasma membrane and how this in turn regulates ligand binding capacity of EGFR. We also examine signals activated downstream of EGFR, finding new spatial organization of phosphoinositide dynamics and other signals leading to activation of Akt within clathrin structures at the plasma membrane. This represents a new direct signaling role for clathrin assemblies at the cell surface, which were known until now largely as endocytosis portals. This work this reveals new insights into the nanoscale spatial organization and regulation of key signals that drive tumor progression.

HOST: Sergey Plotnikov

LOCATION: Cell and Systems Biology, 25 Harbord Street, Suite 432

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