RUI: Probing Intracellular Trafficking Decisions using Quantitative Fluorescence Microscopy and Biochemical Methods

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All eukaryotic cells must make trafficking decisions to maintain optimal distribution of transmembrane or membrane-associated proteins in response to physiological conditions. While a number of signaling pathways and essential trafficking proteins have been described, the information on how trafficking decisions are made is limited. This project will study an area of great interest in the trafficking field, which is the role of copper metabolism gene murr1 domain protein in regulating copper transport. The results of this study are potentially significant for understanding trafficking of other membrane proteins. The societal impacts of this project are educational, and aim to build training opportunities in molecular and cellular biosciences at University of Alaska-Anchorage (UAA), for which there is a high demand, yet limited capacity. This project will build an integrated research and education program at UAA and enhance training opportunities for undergraduate students in research. Undergraduate students will participate directly in the discovery process while gaining experience with advanced scientific concepts, including quantitative biological sciences. The research results of this project will be directly integrated into classroom activities in an inquiry-based cell biology course.All eukaryotic cells must balance outflow trafficking of membrane proteins and lipids towards the plasma membrane with retrograde trafficking towards the Golgi. While a number of signaling pathways and essential trafficking proteins have been studied, the information on how cells integrate diverse signals to make retrograde trafficking decisions is yet to be elucidated. COMMD1 (copper metabolism gene murr1 domain) is the founding member of a family of proteins that influences trafficking and stability of membrane proteins involved in sodium, chloride, and copper transport. Copper is an important part of specific enzymes that maintain normal cell functions. This project aims to understand the role of COMMD1 as an adaptor protein in regulating trafficking of a copper ATPase, which has an important role in copper transport. A set of quantitative biochemical and biophysical techniques, including fluorescence microscopy, colocalization studies, and molecular modeling of protein 3D structures will be employed. These results are potentially significant for understanding the retrograde trafficking of other membrane proteins.