Antagonistic regulation of neurite morphology through Gq/G 11 and G12/G13

Abstract

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 Gαq/Gα11 or Gα12/Gα13, we show here that G 12/G13-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 G13, whereas thrombin effects required G12. Surprisingly, lack of Gαq/ Gα11 resulted in overshooting responses to both stimuli, indicating that Gq/G11-mediated signaling most likely via activation of Rac antagonizes the effects of G12/G13. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.