Figure 6.

Schematic representation of RyR-dependent signaling pathway that mediates PCB-induced and activity-dependent dendritic growth. In the context of activity-dependent dendritic growth, RyR1 and RyR2 in the endoplasmic reticulum of the dendrite functionally link Ca²⁺ influx via NMDA and AMPA receptors to Ca²⁺ release from intracellular stores. Increased intracellular Ca²⁺ as a consequence of RyR activation sequentially activates the CaMKK–CaMK–Ras–MEK/ERK–CREB–Wnt2 signaling pathway to promote dendritic growth. Abbreviations: AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; βCat, β-catenin; Friz, frizzled, the cognate receptor for Wnt2; Ip₃, inositol 1,4,5-triphosphate; mGlu, metabotropic glutamate; PMCA, plasma membrane calcium ATPase; R, receptor; VGCC, voltage-gated Ca²⁺ channel.