Constitutively Active Gα12, Gα13, and Gαq Induce Rho-dependent Neurite Retraction through Different Signaling Pathways

摘要: In neuronal cells, activation of a certain heterotrimeric G protein-coupled receptor causes neurite retraction and cell rounding via the small GTPase Rho. However, specific proteins that mediate Rho-dependent have not yet been identified. Here we investigated effects expression constitutively active Galpha subunits on morphology differentiated PC12 cells. Expression GTPase-deficient Galpha12, Galpha13, Galphaq, but Galphai2, caused in These morphological changes induced by Galphaq were completely inhibited C3 exoenzyme, which specifically ADP-ribosylates inactivates The tyrosine kinase inhibitor tyrphostin A25 blocked Galpha13 Galphaq. failed to inhibit Galpha12-induced changes. On other hand, inhibition protein C or elimination extracellular Ca2+ whereas Galpha12 did require Ca2+. results demonstrate induces cells through different signaling pathways.