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Science 292 (5515): 293-297

Copyright © 2001 by the American Association for the Advancement of Science

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

Trillium Blackmer,13 Eric C. Larsen,5 Michiko Takahashi,2 Thomas F. J. Martin,5 Simon Alford,24* Heidi E. Hamm13*dagger

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 beta gamma subunits (Gbeta gamma ) mimics serotonin's inhibitory effect on neurotransmission. Release of free Gbeta gamma was critical for this effect because a Gbeta gamma scavenger blocked serotonin's effect. Gbeta gamma 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 Gbeta gamma effector pathways. Thus, Gbeta gamma blocked neurotransmitter release downstream of Ca2+ entry and may directly target the exocytotic fusion machinery at the presynaptic terminal.

1 Department of Molecular Pharmacology and Biological Chemistry,
2 Department of Physiology,
3 Northwestern University Institute for Neuroscience, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA.
4 Department of Biological Sciences, University of Illinois at Chicago, 840 West Taylor Street, Chicago, IL 60608, USA.
5 Department of Biochemistry, University of Wisconsin at Madison, Madison, WI 53706, USA.
*   To whom correspondence should be addressed. E-mail: sta{at} (S.A.) and heidi.hamm{at} (H.E.H.)

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

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