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The Journal of Neuroscience, March 15, 2000, 20(6):2131-2141
The Neuronal Monoamine Transporter VMAT2 Is Regulated by the
Trimeric GTPase Go2
Markus
Höltje1,
Burkhard
von Jagow1,
Ingrid
Pahner1,
Marion
Lautenschlager2, 3,
Heide
Hörtnagl2,
Bernd
Nürnberg4,
Reinhard
Jahn5, and
Gudrun
Ahnert-Hilger1
1 Institut für Anatomie, 2 Institut
für Pharmakologie, and 3 Neurologische
Universitätsklinik der Charité, Humboldt-Universität
zu Berlin, 10115 Berlin, Germany, 4 Institut für
Pharmakologie der Freien Universität Berlin, 14195 Berlin,
Germany, and 5 Max-Planck-Institut für
Biophysikalische Chemie, 37077 Göttingen, Germany
Monoamines such as noradrenaline and serotonin are stored in
secretory vesicles and released by exocytosis. Two related monoamine transporters, VMAT1 and VMAT2, mediate vesicular transmitter uptake. Previously we have reported that in the rat pheochromocytoma cell line
PC 12 VMAT1, localized to peptide-containing secretory granules, is
controlled by the heterotrimeric G-protein Go2. We now show that in BON cells, a human serotonergic neuroendocrine cell line derived from a pancreatic tumor expressing both transporters on large,
dense-core vesicles, VMAT2 is even more sensitive to G-protein regulation than VMAT1. The activity of both transporters is only downregulated by G o2, whereas comparable
concentrations of Go1 are without effect. In
serotonergic raphe neurons in primary culture VMAT2 is also
downregulated by pertussis toxin-sensitive Go2. By electron
microscopic analysis from prefrontal cortex we show that VMAT2 and
Go2 associate preferentially to locally recycling small
synaptic vesicles in serotonergic terminals. In addition, Go2-dependent modulation of VMAT2 also works when using a
crude synaptic vesicle preparation from this brain area. We conclude that regulation of monoamine uptake by the heterotrimeric G proteins is
a general feature of monoaminergic neurons that controls the content of
both large, dense-core and small synaptic vesicles.
Key words:
VMAT2; Go2; neuroendocrine cells; neurons; transmitter uptake; vesicular plasticity
Copyright © 2000 Society for Neuroscience 0270-6474/00/2062131-11$05.00/0
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