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 Galpha(q)/Galpha(11) or Galpha(12)/Galpha(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 Galpha(q)/Galpha(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).
Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, D-69120 Heidelberg, Germany.
Alexander
A
Nürnberg
Anja U
AU
Braüer
Nina
N
Wettschureck
Stefan
S
Offermanns
D000818:Animals; D002478:Cells, Cultured; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016501:Neurites / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D044365:GTP-Binding Protein alpha Subunits, G12-G13; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020744:rac GTP-Binding Proteins