FIGURE 9.

Schematic of coordinate PACAP receptor signaling for sympathetic neuronal survival. The ability for the PAC₁ receptor to engage Gα_s/Gα_q signaling pathways represents a multifaceted but coordinate means for neurotrophic signaling. PAC₁ receptor Gα_s signaling in sympathetic neurons can stimulate cAMP mechanisms to promote sustained ERK activation. In addition to rapid PAC₁ receptor-mediated Gα_q activation of phospholipase C /PKC pathways, the internalization of PAC₁ receptors through clathrin-coated vesicles may facilitate scaffold assembly to engage PI3kγ/Akt signaling for survival mechanisms. Whether ERK, Akt, or other PAC₁ receptor-stimulated mechanisms attenuate JNK/p38 MAPK activation after NGF-deprivation remains to be elucidated. PDK, phosphoinositide-dependent protein kinase; AC, adenylyl cyclase.