AbstractRecent experiments in various cell types such as mammalian neutrophils and Dictyostelium discoideum amoebae point to a key role for the lipid product of PI 3‐kinase, PIP3, in determining internal polarity. In neurons, as a consequence of the elongation of one neurite, the axon is specified and the cell acquires its polarity. To test the hypothesis that PI 3‐kinase and PIP3 may play a role in neuronal polarity, and especially in axon specification, we observed localization of PIP3 visualized by Akt‐PH‐GFP in developing hippocampal neurons. We found that PIP3 accumulates in the tip of the growing processes. This accumulation is inhibited by addition of PI 3‐kinase inhibitors. Those inhibitors, consistently with a role of PIP3 in process formation and elongation, delay the transition from stage 1 neurons to stage 3 neurons, and both axon formation and elongation. Moreover, when the immature neurite contacts a bead coated with laminin, a substrate known to induce axon specification, PIP3 accumulates in its growth cone followed by a rapid elongation of the neurite. In such conditions, the addition of PI 3‐kinase inhibitors inhibits both PIP3 accumulation and future axon elongation. These results suggest that PIP3 is involved in axon specification, possibly by stimulating neurite outgrowth. In addition, when a second neurite contacted the beads, this neurite rapidly elongates whereas the elongation of the first laminin‐contacting neurite stops, consistently with the hypothesis of a negative feedback mechanism from the growing future axon to the other neurites.

Ménager, C., Arimura, N., Fukata, Y., & Kaibuchi, K. (2004). PIP3 is involved in neuronal polarization and axon formation. Journal of Neurochemistry, 89(1), 109–118. Portico.