Mediation of PACAP-like neuropeptide transmission by coactivation of Ras/Raf and cAMP signal transduction pathways in Drosophila

Nature. 1995 Jun 15;375(6532):588-92. doi: 10.1038/375588a0.


Much work on the signal transduction mechanisms underlying neurotransmission has been directed towards studying the roles of the cyclic AMP and phosphoinositide pathways. Upon ligand binding, the transmitter receptors interact with heterotrimeric G proteins, allowing G alpha and G beta gamma subunits to disengage. The free G alpha then modulates the activity of adenylyl cyclase and phospholipase C. It has been suggested that the G beta gamma complex which is activated through muscarinic or neuropeptide receptors can stimulate mitogen-activated protein kinase (MAPK) via activation of the small guanine-nucleotide-binding protein Ras. Sequential activation of the intermediates in the Ras/Raf serine-threonine protein kinase/MAPK kinase/MAPK/transcription factor pathway has emerged as a central mechanism for controlling cell proliferation and differentiation in yeast, worms, fruitflies and mammals. Here we show, by analysis of Drosophila mutants, that synaptic current and modulation of K+ current, triggered by a pituitary adenylyl cyclase-activating polypeptide-like neuropeptide, are mediated by coactivation of the Ras/Raf and Rutabaga-adenylyl cyclase pathways. Thus the Ras/Raf pathway also appears to be essential for G-protein-coupled neurotransmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism
  • Animals
  • Cyclic AMP / metabolism*
  • Drosophila
  • GTP-Binding Proteins / metabolism
  • Mutation
  • Neuropeptides / metabolism*
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Potassium / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-raf
  • Signal Transduction*
  • ras Proteins / metabolism*


  • Neuropeptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Proto-Oncogene Proteins
  • Cyclic AMP
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • GTP-Binding Proteins
  • ras Proteins
  • Adenylyl Cyclases
  • Potassium