Figure 12.

Schematic diagram of the pathways involved in PbTx-2-induced neurite outgrowth. PbTx-2 actions cause increased spontaneous Ca²⁺ oscillations, which lead to the presynaptic release of glutamate. This glutamate release produces an increase in Ca²⁺ influx through NMDARs, leading to the activation of CaMKII and the small G-protein Rac, which, in turn, activates its downstream effector PAK1. The activated Pak1 engages the cofilin cycle, resulting in changes in F-actin filaments, with attendant increases in neurite outgrowth. Abbreviations: VGSC: voltage-gated sodium channels, GluN2B: N-methyl-D-aspartate receptor subtype 2B, CaMKII: Ca²⁺/calmodulin-dependent kinase II; GEF: guanine-nucleotide-exchange factor; PAK1: p21 protein (Cdc42/Rac)-activated kinase1.