G Protein βγ Subunit-Mediated Presynaptic Inhibition: Regulation of Exocytotic Fusion Downstream of Ca2+ Entry

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Science  13 Apr 2001:
Vol. 292, Issue 5515, pp. 293-297
DOI: 10.1126/science.1058803

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The nervous system can modulate neurotransmitter release by neurotransmitter activation of heterotrimeric GTP–binding protein (G protein)–coupled receptors. We found that microinjection of G protein βγ subunits (Gβγ) mimics serotonin's inhibitory effect on neurotransmission. Release of free Gβγ was critical for this effect because a Gβγ scavenger blocked serotonin's effect. Gβγ had no effect on fast, action potential–evoked intracellular Ca2+ release that triggered neurotransmission. Inhibition of neurotransmitter release by serotonin was still seen after blockade of all classical Gβγ effector pathways. Thus, Gβγ blocked neurotransmitter release downstream of Ca2+ entry and may directly target the exocytotic fusion machinery at the presynaptic terminal.

  • * To whom correspondence should be addressed. E-mail: sta{at} and heidi.hamm{at} (H.E.H.)

  • Present address: Department of Pharmacology, 442 Robinson Research Building, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

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