Role of myosin 1e in podocyte biology and renal filtration

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Modified Project Summary/Abstract Section Disruption of normal glomerular filtration is one of the key causes of end-stage renal disease, leading to the need for renal replacement therapy. Myosin 1e (Myo1e) is a cytoskeletal protein that is highly expressed in the glomerular epithelial cells (podocytes) and is involved in many processes important for podocyte function, such as actin assembly regulation, endocytosis, and regulation of cell adhesion. Mutations in MYO1E are found in patients with chronic kidney disease, highlighting its role in maintaining glomerular filtration barrier. In this project we will examine the role of Myo1e activity in supporting podocyte cytoskeletal organization and normal kidney function and test the hypothesis that activation of Myo1e can help protect podocytes from injury and preserve normal glomerular filtration. In Aim 1 we will analyze how disease-associated mutations affect Myo1e functions and activity using a combination of cell-based and in vitro (biochemical) methods. In Aim 2 we will determine the mechanism of autoinhibition of Myo1e activity. In Aim 3 we will test how Myo1e activity helps maintain podocyte integrity and whether activation of Myo1e will have a protective effect on kidney function.