Podocytes play a key role in the pathogenesis of glomerular diseases. They exhibit a complex morphology with specialized cellular projections, between which the intercellular contact—the slit diaphragm—is located. This structure is essential for the functional integrity of the glomerular filtration barrier. Neurons also possess highly differentiated cellular extensions, whose development is directed by extracellular “guidance cues” that act through specific neuronal receptors.

Many of these guidance cues are also expressed in podocytes and are involved in the development and disease-associated remodeling of podocyte processes. The neurotrophic receptor tyrosine kinase 3 (Ntrk3) is one such neuronal guidance receptor expressed in podocytes. We have shown that Ntrk3 can transmit signals to the actin cytoskeleton of cultured podocytes via Erk- and WAVE2-dependent pathways (Gromnitza et al., FASEB J, 2018). This signaling cascade leads to enhanced podocyte migration.

In this research project, we will investigate the role of Ntrk3 in podocytes in vivo using tissue-specific mouse models and characterize the underlying molecular mechanisms in podocyte culture systems.

(DFG project number 447767934).