Cell organization and polarized trafficking
Speaker : Dr David Murray, Principal Investigator and Sir Henry Dale Fellow, School of Life Sciences, University of Dundee
11th March 2024, 1 pm, Lecture Theatre C, School of Physics and Astronomy
Metazoan are characterized by tissue composed of organized arrangements of specialized cells. The logistics and organization of tissue structures are heavily dependent on distinct aspects of trafficking. Specifically, polarized trafficking is required for the cell structures responsible for tissue generation and maintenance, and can be reprogrammed with changes to membrane dynamics. In this pathway, the conserved molecular machinery of the exocyst integrates signaling from lipid and protein regulatory factors. This activity results in tethering vesicles to the plasma membrane for their eventual fusion and cargo delivery. However, the molecular mechanisms of this process are poorly defined. To determine the mechanics and regulation of tethering in polarized trafficking, we have reconstituted the system harnessing protein biochemistry, membrane biophysical, and experimental cell biology approaches. Our data provide a molecular mechanism of exocyst-mediated tethering, and a unique functional requirement for phosphoinositide signaling on late-stage vesicles in the vicinity of the plasma membrane. To address polarized trafficking in the context of cell organizational processes, we examine the reprogramming of exocyst regulation in epithelial to mesenchymal transition. This process requires remodeling the membranes and polarity of the cell, and we focus on differential regulatory factors in this regime, including organizers of secretion sites. Altogether, our long-term goal is to identify principles holistically linking the programming of molecular mechanism to outcomes at a tissue scale.