Podocyte Development and Function Are Dependent on Endophilin

Endophilin is critical to the development and maintenance of podocyte function in the kidney. This is the conclusion of Keita Soda, PhD, and co-workers from Yale University, who presented work at the Hot Science session at Kidney Week 2012 that described the connection between the protein endophilin and the synaptic proteins dynamin and synpatojanin 1, as well as the vital role endophilin plays in the formation and maintenance of the glomerular filtration barrier.

Expanding on their previous investigation of synaptic proteins, Soda and co-workers tried to determine the function of clathrin-coated pits that are seen in the podocyte foot processes.

They hypothesized that endophilin may play a role in podocyte function.

“Endophilin interacts with CD2AP, a critical protein which when lost in mice or mutated in humans results in nephrotic syndrome,” Soda said. “Morever, it interacts with dynamin and synaptojanin, which when also deleted in mice results in severe proteinuria. This made endophilin an attractive candidate.”

Soda and colleagues used fluorescent images to demonstrate that endogenous endophilin colocalized with podocyte marker-nephrin in glomeruli. The protein was also found in late-stage clathrin-coated pits with F-actin, dynamin, and synaptojanin 1, verifying endophilin’s role in maintaining the glomerular filtration barrier. A second experiment comparing triple knockout mice (bred lacking all three isoforms of endophilin) with wild type mice found the knockout mice had a significantly high level of proteinuria, as well as dilated tubules and accumulation of mesangial matrix in glomeruli.

When asked if the confirmation of endophilin’s role in podocyte functioning could lead to potential targets for treating nephrotic syndrome, Soda said that “stabilizing endocytic pathways regulated by endophilin/synaptojanin or dynamin may result in possible therapeutic interventions, but one must be cognizant as not all mechanisms of nephrotic syndrome are identical,” Soda said, concluding “further investigation and research will be required.”

December 2012 (Vol. 4, Number 12)