|
|
|
|
|
| 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] | |
|
|
|
The scope and number of records on eDoc is subject
to the collection policies defined by each institute
- see "info" button in the collection browse view.
|
|
Advanced