DEFINING THE MECHANISMS BY WHICH TRIM9, A UBIQUITIN LIGASE, MEDIATES INNATE IMMUNE CELL FUNCTIO
Amanda Kortum, North Carolina State University College of Veterinary Medicine
Amanda N. Kortum, Debra Tokarz, Jeffrey A. Yoder
Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University College of Veterinary Medicine, 1060 William Moore Drive, Raleigh, NC 27607 USA
The persistence of an immune response can contribute to the development of disease states, amplifying the extent of tissue damage or perpetuating the disease condition. Damaging inflammatory states are often characterized by high numbers of macrophages and neutrophils. Studying the cellular mechanisms required for phagocyte migration to sites of inflammation will elucidate how these pathways could be therapeutically targeted for disruption during persistent, harmful inflammation. Preliminary data identifies a novel role for the E3 ubiquitin ligase Tripartite Motif Containing 9 (TRIM9) as a critical mediator of macrophage motility in the zebrafish model. This is in agreement with the well-defined role TRIM9 plays in mediating neuronal axon migration in mammals. While several members of the TRIM family have known regulatory roles in the NFκB and interferon signaling pathways through interactions with a wide range of substrates, the functional roles of TRIM9 in immune cells are currently undefined. We hypothesize that TRIM9 plays a critical role in multiple immune functions by mediating a novel phagocyte-specific ubiquitin pathway. For this work, we will determine which phagocyte immune functions, such as migration and phagocytosis, are mediated by TRIM9 and begin to define the TRIM9 protein interactome. This research will begin to define the immunologically relevant cellular and molecular processes mediated by TRIM9 and its protein network in mammalian phagocytes and contribute to an area of research that has great potential for producing targeted therapeutics for conditions where persistent inflammatory states contribute to the disease process.