Go protein as signal transducer in the pertussis toxin-sensitive phosphatidylinositol pathway.
Receptors stimulating phospholipase C do so through heterotrimeric GTP-binding proteins to produce two second messengers, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol. In spite of the detailed understanding of phospholipase C structure and phosphatidyl inositol signalling, the identity of the GTP-binding protein involved is so far unknown. To address this issue, we have used the Xenopus oocyte in which muscarinic receptors couple to phospholipase C through a pertussis toxin-sensitive GTP-binding protein. In this cell, InsP3 mobilizes intracellular Ca2+ to evoke a Cl- current. The magnitude of this Cl- current is proportional to the amount of InsP3 in the cell, and therefore can be used as an assay for InsP3 production. We report here that the activated alpha-subunit of the GTP-binding protein GO, when directly injected into oocytes, evokes a Cl- current by mobilizing Ca2+ from intracellular InsP3-sensitive stores. We also show that holo-GO, when injected into oocytes, can specifically enhance the muscarinic receptor-stimulated Cl- current. These data indicate that GO can serve as the signal transducer of the receptor-regulated phospholipase C in Xenopus oocytes.
Moriarty
T M
TM
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029.
Padrell
E
E
Carty
D J
DJ
Omri
G
G
Landau
E M
EM
Iyengar
R
R
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D008845:Microinjections; D009865:Oocytes; D037342:Pertussis Toxin; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction; D013873:Thionucleotides / Q000494:pharmacology; D010738:Type C Phospholipases / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D014982:Xenopus laevis
D002712:Chlorides; D011976:Receptors, Muscarinic; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium