Antagonistic Regulation of Neurite Morphology through Gq/G11 and G12/G13

The induction of neurite retraction and growth cone collapse via G-protein-coupled receptors is involved in developmental as well as regenerative processes. The role of individual G-protein-mediated signaling processes in the regulation of neurite morphology is still incompletely understood. Using primary neurons from brains lacking G alpha(q)/G alpha(11) or G alpha(12)/G alpha(13), we show here that G(12)/G(13)-mediated signaling is absolutely required for neurite retraction and growth cone collapse induced by the blood-borne factors lysophosphatidic acid and thrombin. Interestingly, the effects of lysophosphatidic acid were mediated mainly by G(13), whereas thrombin effects required G(12). Surprisingly, lack of G alpha(q)/G alpha(11) resulted in overshooting responses to both stimuli, indicating that G(q)/G(11)-mediated signaling most likely via activation of Rac antagonizes the effects of G(12)/G(13).