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Smo regulates the actin cytoskeleton through the small GTPases RhoA and Rac1. This regulation occurs in a context-specifi c manner, through Gi proteins and PI3K in fi broblasts, and through Tiam1 or through the Src kinase family (SFK) members Src and Fyn in neurons. In addition, Smo stimulates calcium release from the endoplasmic reticulum (ER) in spinal neurons through Gi and PLC-γ–catalyzed generation of IP3 and opening of IP3-dependent channels.
