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Characterization of Nephrin clusters with an inducible phosphorylation system

Soyeon Kim Research Image

Recent studies in our lab have demonstrated that the podocyte protein Nephrin and its downstream signaling molecules Nck and N-WASP can undergo phase transitions in vitro from small complexes to micron-sized polymers via multi-valent interactions.

My current project follows from this work to examine the hypothesis that multi-valent interaction between Nephrin, Nck and N-WASP produce phosphorylation-mediated phase transitions in mammalian cells, which can induce local rearrangement in the actin cytoskeleton. To study this process I developed a new method to induce the phosphorylated state of Nephrin in cells. I have found that phosphorylation triggers the formation of microdomains enriched in Nephrin at the plasma membrane.

I am currently investigating the dynamics and activity of proteins within the observed microdomains. This work will not only elucidate the mechanism used by podocyte proteins to stimulate localized actin rearrangements, but will also further our understanding of how multi-valent interactions between proteins in general can contribute to spatiotemporal regulation of cellular signaling.