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          Institute: MPI für molekulare Genetik     Collection: Department of Human Molecular Genetics     Display Documents



  history
ID: 191983.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
The vesicular monoamine content regulates VMAT2 activity through Gq in mouse platelets
Authors:Höltje, Markus; Winter, Sandra; Walther, Diego; Pahner, Ingrid; Hörtnagl, Heide; Ottersen, Ole Peter; Bader, Michael; Ahnert-Hilger, Gudrun
Language:English
Date of Publication (YYYY-MM-DD):2003-05
Title of Journal:Journal of Biological Chemistry
Journal Abbrev.:J Biol Chem
Volume:278
Issue / Number:18
Start Page:15850
End Page:15858
Copyright:© 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
Review Status:not specified
Audience:Experts Only
Abstract / Description:Variations in the neurotransmitter content of secretory vesicles enable neurons to adapt to network changes. Vesicular content may be modulated by vesicle-associated Go2, which down-regulates the activity of the vesicular monoamine transmitter transporters VMAT1 in neuroendocrine cells and VMAT2 in neurons. Blood platelets resemble serotonergic neurons with respect to transmitter storage and release. In streptolysin O-permeabilized platelets, VMAT2 activity is also down-regulated by the G protein activator guanosine 5'-(i-imido)triphosphate (GMppNp). Using serotonin-depleted platelets from peripheral tryptophan hydroxylase knockout (Tph1/) mice, we show here that the vesicular filling initiates the G protein-mediated down-regulation of VMAT2 activity. GMppNp did not influence VMAT2 activity in naive platelets from Tph1/ mice. GMppNp-mediated inhibition could be reconstituted, however, when preloading Tph1/ platelets with serotonin or noradrenaline. Gq mediates the down-regulation of VMAT2 activity as revealed from uptake studies performed with platelets from Gq deletion mutants. Serotonergic, noradrenergic, as well as thromboxane A2 receptors are not directly involved in the down-regulation of VMAT2 activity. It is concluded that in platelets the vesicle itself regulates transmitter transporter activity via its content and vesicle-associated Gq.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:Institut für Anatomie der Charité, Humboldt Universität zu Berlin, Philippstrasse 12, 10115 Berlin, Germany,
Max-Delbrück-Centrum für Molekulare Medizin, 13092 Berlin Buch, Germany,
Centre for Molecular Biology and Neuroscience and Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, P. O. Box 1105, Blindern, N-0317 Oslo, Norway,
Institut für Pharmakologie der Charité, Humboldt Universität zu Berlin, Dorotheenstr. 94, 10117 Berlin, Germany
Identifiers:ISSN:0021-9258 [ID No:1]
ISSN:1083-351X [ID No:2]
DOI:10.1074/jbc.M212816200 [ID No:3]
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