Seminar Event Detail


Mathematical Biology

Date:  Monday, September 11, 2017
Location:  335 West Hall (12:00 PM to 1:00 PM)

Title:  Systems analysis of clathrin-mediated endocytosis

Abstract:   There is a growing body of evidence suggesting that clathrin-mediated endocytosis (CME) is dysregulated in cancer. CME is not only the major route for receptor ligand uptake but also a dynamic plasma membrane process that is highly integrated into signal transduction pathways. In addition to hyperactive signaling in cancer cells, they also exhibit markedly different biomechanical properties. My lab is interested in studying the mechanochemical responses of biological systems. I will present our projects on the regulation of CME in this context. We are interested in how physical cues might influence the dynamics of clathrin-coated pits, the fundamental functional unit of CME. Combining live cell imaging, high content image analysis, and micro-patterned surfaces of different sizes to control the cell spreading sizes and hence cell tension, we found that increasing cell spreading increased CCP initiation and the proportions of short-lived, and likely abortive, CCPs. By analyzing fluorescence intensities of CCPs under different conditions, we discovered that cortical tension regulates the size of individual CCPs. We further went on to characterize the dynamics of CCPs in breast cell lines with increasing metastatic potential and revealed the tumor suppressor protein PTEN as a key regulatory protein that in part contributes to these dynamic differences. When endocytosis is inhibited, while Akt signaling is upregulated, mTOR signaling becomes downregulated. Finally, we are using spatially resolved proteomics by engineered ascorbate peroxidase to unravel the dynamic interactome of chemokine receptor CXCR4 during ligand-induced endocytosis. Together, our study reveals new mechanistic insights into how cell tension regulates the dynamics of CCPs and the interconnection between endocytosis and cell signaling.

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Speaker:  Allen Liu
Institution:  University of Michigan, Mechanical Engineering

Event Organizer:   Victoria Booth    vbooth@umich.edu

 

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