Uncovering the Podocyte Foot Process Proteome

Podocytes are highly specialized epithelial cells of the kidney glomerulus. Podocytes’ long protrusions, called foot processes, connect to each other at specialized junctions called slit diaphragms (SD), which are essential for the filtration function of the glomerulus. Glomerular breakdown primarily due to podocyte integrity loss is the most common clinical observation in kidney disease. Due in part to the inaccessibility of the SD to conventional biochemical methods, only a small number of proteins are known to localize to the SD. We hypothesize that unidentified components of the slit diaphragm are integral to podocyte integrity and kidney function. Proximity-Dependent Biotin Identification (BioID) was used to determine proteins associated with endogenous podocin/NPHS2, a well-documented SD protein. We identified an Immunoglobulin-like domain-containing receptor 2 (Ildr2) and a Formin-binding protein 1-like (Fnbp1l) as two novel proteins of the podocyte foot process. Recent data from sc-RNAseq databases suggest that Ildr2 is expressed in human podocytes, localizes in the SD, and plays a crucial role in podocyte integrity. Ongoing work aims to test the importance of these factors in vertebrate kidney function. By investigating the cellular role of SD proteins such as Ildr2 and Fnbp1l, we can better understand the causes of renal disease at the molecular level.Bachelor of Scienc