GAP-43 augments G protein-coupled receptor transduction in Xenopus laevis oocytes.
The neuronal protein GAP-43 is thought to play a role in determining growth-cone motility, perhaps as an intracellular regulator of signal transduction, but its molecular mechanism of action has remained unclear. We find that GAP-43, when microinjected into Xenopus laevis oocytes, increases the oocyte response to G protein-coupled receptor agonists by 10- to 100-fold. Higher levels of GAP-43 cause a transient current flow, even without receptor stimulation. The GAP-43-induced current, like receptor-stimulated currents, is mediated by a calcium-activated chloride channel and can be desensitized by injection of inositol 1,4,5-trisphosphate. This suggests that neuronal GAP-43 may serve as an intracellular signal to greatly enhance the sensitivity of G protein-coupled receptor transduction.
Strittmatter
S M
SM
Developmental Biology Laboratory, Massachusetts General Hospital, Charlestown.
Cannon
S C
SC
Ross
E M
EM
Higashijima
T
T
Fishman
M C
MC
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D018118:Chloride Channels; D005260:Female; D019922:GAP-43 Protein; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D014982:Xenopus laevis
D018118:Chloride Channels; D019922:GAP-43 Protein; D006133:Growth Substances; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; D015544:Inositol 1,4,5-Trisphosphate; D019204:GTP-Binding Proteins; D000109:Acetylcholine; D002118:Calcium