Researcher(s)
- Jack Mason, Biological Sciences, University of Delaware
Faculty Mentor(s)
- Velia Fowler, Biological Sciences, University of Delaware
Abstract
Almost every organ in the body requires a constant blood supply. However, red blood cells only live for around 120 days, meaning our body has to constantly replenish them. Red blood cells are made via a process called erythropoiesis. Erythropoiesis, or red blood cell differentiation, occurs primarily in the bone marrow of adults and is important to maintain a sufficient blood supply.
Red blood cells are unique from other cells because they don’t have any internal organelles, including nuclei. Immature red blood cells, known as erythroblasts, must get rid of their nuclei in order to store more oxygen-carrying hemoglobin. Our lab is interested in how the protein F-actin, as well as other actin-binding proteins, facilitate this enucleation event, giving rise to mature red blood cells.
Tensin-1 (TNS1) is an actin-binding protein that is typically found in focal-adhesion complexes which are necessary for connecting the internal actin cytoskeleton to the extracellular matrix. The full length TNS1 protein has a predicted molecular weight of 185 kDa. Previous research conducted by our lab reveals a short isoform of Tensin-1 (e-TNS1) which has a crucial role in the terminal differentiation of immature red blood cells. CRISPR-Cas9 gene editing in which e-TNS1 was deleted shows a dramatic decrease in enucleation efficiency. This isoform is missing the first 889 amino acids, with a predicted molecular weight of 125 kDa, noticeably different from the full length tensin protein.
The focus of this project is to further develop our understanding of e-TNS1 by searching other tissue types for significant levels of this isoform. Western blots were used to analyze e-TNS1 expression in various mouse tissues. Significant amounts of e-TNS1 were not found in any other tissue types, indicating it is unique to erythroblasts, which makes sense considering they are the only cell type that expels its nucleus. Based on our findings, we hope to develop an e-TNS1 knockout mouse to help further understand the function of this protein.