Abstract
MUCH work on the signal transduction mechanisms underlying neurotransmission has been directed towards studying the roles of the cyclic AMP and phosphoinositide pathways1–3. Upon ligand binding, the transmitter receptors interact with heterotrimeric G proteins, allowing Gα and Gβγ subunits to disengage2,3. The free Gα then modulates the activity of adenylyl cyclase and phospholipase C1–3. It has been suggested that the Gβγ 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 Ras4,5. 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 mammals6–11. 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 neuropeptide12, are mediated by coactivation of the Ras/Raf and Ruta-aga–adenylyl cyclase pathways. Thus the Ras/Raf pathway also appears to be essential for G-protein-coupled neurotransmission.
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Zhong, Y. Mediation of PACAP–like neuropeptide transmission by coactivation of Ras/Raf and cAMP signal transduction pathways in Drosophila. Nature 375, 588–592 (1995). https://doi.org/10.1038/375588a0
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DOI: https://doi.org/10.1038/375588a0
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