Structure and Functions of ER/Plasma Membrane Junctions

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Endoplasmic reticulum/plasma membrane (ER/PM) junctions are known to be sites of calcium ion (Ca2+) influx. Recently, the PI discovered that these junctions function as trafficking hubs for insertion and removal of plasma membrane proteins. Furthermore, the PI has found that the voltage gated potassium channel Kv2.1 interacts with the endoplasmic reticulum, dramatically increasing ER/PM junction surface area and structurally changing the junction morphology. The PI's findings show that the Kv2.1 potassium channel remodels to cortical ER, which is likely within 30 nm of the plasma membrane. Kv2.1 is playing a structural role similar to that of Orai, for the PI proposes that Kv2.1 is binding an ER membrane protein. Thus, Kv2.1-mediated ER enrichment on the cell surface is a novel specialized organelle with specific functions in protein transport vital to cell signaling. The current project focuses on understanding the biology of ER/PM junctions with particular emphasis on the regulation of the ER/PM junction structure and its function in the modulation of membrane protein trafficking. The PI will answer the following questions: What is the role of Kv2.1 in protein trafficking at ER/PM junctions? How are ER/PM junctions dynamically regulated by Kv2.1? What are the relationships between the cortical cytoskeleton, ER, and Kv2.1? Which theoretical framework can be used to describe the assembly and maintenance of these domains? How does large-scale membrane behavior emerge from the interactions between Kv2.1 and ER? The fusion of multicolor single-molecule tracking in living cells and advanced stochastic process analysis, which are integral to the project, will provide answer to these questions. This research will offer excellent opportunities for graduate and undergraduate student participation in interdisciplinary research through the collaboration between two laboratories with very different backgrounds. The research program will be integrated with an outreach component by developing a microscopy laboratory for students at a local elementary school. The goal of the outreach program is to foster scientific enquiry and to motivate students to appreciate science from an early age. This lab presents a unique opportunity to leverage integration of education and research, giving students access to hands-on practical learning.This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Cellular Dynamics and Function Program in the Division of Molecular and Cellular Biosciences.