Figure 8.

A proposed model for podoplanin signaling in the brain neurons. Extracellular NGF (1) binds to LRR or Ig-like domains of its canonical TrkA receptor (2) (it can also bind to p75 receptors not represented here) to induce well established CREB-mediated neuritic outgrowth important for synaptic plasticity and learning and memory. Concomitantly, extracellular NGF (1) can physically interact with podoplanin (3) to modulate podoplanin-related signaling via intracellular partners like Ezrin (4) to promote cytoskeleton reorganization and hence neuritic protrusion or retraction thus affecting the synaptic function. Whether podoplanin can also directly interact with TrkA receptors (“?” in the figure) thus affecting NGF/TrkA-mediated CREB signaling or whether podoplanin may, on its own ability, affect NGF-mediated CREB signaling (5) via a NGF/podoplanin signaling pathway (“??” in the figure) remains to be characterized.