Regulation of Vesicular Monoamine and Glutamate Transporters by Vesicle-Associated Trimeric G Proteins: New Jobs for Long-Known Signal Transduction Molecules

  • I. Brunk
  • M. Höltje
  • B. von Jagow
  • S. Winter
  • J. Sternberg
  • C. Blex
  • I. Pahner
  • G. Ahnert-Hilger
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 175)

Abstract

Neurotransmitters of neurons and neuroendocrine cells are concentrated first in the cytosol and then in either small synaptic vesicles of presynaptic terminals or in secretory vesicles by the activity of specific transporters of the plasma and the vesicular membrane, respectively. In the central nervous system the postsynaptic response depends—amongst other parameters—on the amount of neurotransmitter stored in a given vesicle. Neurotransmitter packets (quanta) vary over a wide range which may be also due to a regulation of vesicular neurotransmitter filling. Vesicular filling is regulated by the availability of transmitter molecules in the cytoplasm, the amount of transporter molecules and an electrochemical proton-mediated gradient over the vesicular membrane. In addition, it is modulated by vesicle-associated heterotrimeric G proteins, Gαo2 and Gαq. Gαo2 and Gαq regulate vesicularmonoamine transporter (VMAT) activities in brain and platelets, respectively. Gαo2 also regulates vesicular glutamate transporter (VGLUT) activity by changing its chloride dependence. It appears that the vesicular content activates the G protein, suggesting a signal transduction from the luminal site which might be mediated by a vesicular G protein-coupled receptor or as an alternative possibility by the transporter itself. Thus, G proteins control transmitter storage and thereby probably link the regulation of the vesicular content to intracellular signal cascades.

Keywords

Vesicular transmitter transporter G protein Vesicular filling Neurotransmitter Storage 
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Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • I. Brunk
    • 1
  • M. Höltje
    • 1
  • B. von Jagow
    • 1
  • S. Winter
    • 1
  • J. Sternberg
    • 1
  • C. Blex
    • 1
  • I. Pahner
    • 1
  • G. Ahnert-Hilger
    • 1
  1. 1.AG Funktionelle Zellbiologie, Institut für Integrative Neuroanatomie, Centrum für Anatomie, CharitéUniversitätsmedizin BerlinBerlinGermany

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