Investigating intracellular SNARE-mediated trafficking of the kidney slit diaphragm protein nephrin
Year: 2016
Type: dissertation
Abstract: Kidneys are essential organs that act as natural filters to remove waste products from circulating plasma. Blood filtration in the kidney is dependent on podocytes, specialized epithelial cells that contribute to filtration via a molecular complex called the slit diaphragm (SD). The transmembrane protein nephrin is a key structural and signalling component of the SD, and its proper trafficking and expression on the cell surface is required for its function. SNAREs are a large family of proteins found on transport vesicles and target membranes that mediate intracellular trafficking. We hypothesized that nephrin trafficking within podocytes is regulated by SNAREs. The presence of specific SNAREs in the glomeruli was determined via evaluation of the literature, immunostaining of SNAREs in mouse and rat kidneys, and profiling of SNAREs in cultured cell lines, including cultured human podocytes. We demonstrate here that nephrin trafficking is SNARE-mediated as inhibition of all SNARE trafficking pathways showed a reduction of nephrin at the cell surface. We identified 3 SNAREs that co-localize with nephrin, and that Syntaxin4 and SNAP-23 complex with nephrin. We found that both of these latter SNAREs are upregulated in rodent kidney injury models associated with altered nephrin surface expression. As SNARE proteins have not yet been investigated in podocyte biology, these studies provide an entry point to explore how membrane trafficking is regulated during SD development and maintenance.
Author: Rachael E. McNeilly
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2586475042