Cell growth and differentiation in developing tissues are, at first impression, quite different endeavors from readjusting synaptic strength during activity-dependent synaptic plasticity in mature neurons. Nevertheless, it is becoming increasingly clear that these two distinct processes share multiple intracellular signaling events. How these common pathways result in cell division (during proliferation), large-scale cellular remodeling (during differentiation) or synapse-specific changes (during synaptic plasticity) is only starting to be elucidated. Here we review the latest findings on two prototypical examples of these shared mechanisms: the Ras-PI3K pathway and the intracellular signaling elicited by neural cell adhesion molecules interacting with growth factor receptors.
Simplified scheme for the activation and downstream actions of the PIP3 pathway during synaptic plasticity. Upon opening of NMDARs, calcium-sensitive Ras-GRFs nucleotide exchange factors lead to the formation of active Ras, with the concomitant activation of PI3K. This enzyme catalyzes the formation of PIP3, which in turn may act directly on receptor scaffolding complexes, or indirectly, via Akt activation and GSK3β inhibition. Ras also activates ERK–MAPK downstream signaling. These pathways jointly lead to LTP expression. Alternatively, NMDAR can lead to the activation of Rap, for LTD expression. PTEN catalyzes the turnover of PIP3 to form PIP2. Inhibition of Akt and activation of GSK3β will favor LTD induction. In addition, formation of PIP2 will lead to the recruitment of endocytic factors and the internalization of AMPARs for LTD expression.