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The vesicular monoamine content regulates VMAT2 activity through G α(q) mouse platelets - evidence for autoregulation of vesicular transmitter update

Item Type:Article
Title:The vesicular monoamine content regulates VMAT2 activity through G α(q) mouse platelets - evidence for autoregulation of vesicular transmitter update
Creators Name:Holtje, M. and Winter, S. and Walther, D. and Pahner, I. and Hortnagl, H. and Ottersen, O.P. and Bader, M. and Ahnert-Hilger, G.
Abstract: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′-({beta}i{gamma}-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. G{alpha}q mediates the down-regulation of VMAT2 activity as revealed from uptake studies performed with platelets from G{alpha}q 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 G{alpha}q.
Keywords:5-HT2A Serotonin Receptor, Blood Platelets, Gq-G11 GTP-Binding Protein Alpha Subunits, Guanylyl Imidodiphosphate, Heterotrimeric GTP-Binding Proteins, Homeostasis, Membrane Glycoproteins, Membrane Transport Proteins, Neuropeptides, Serotonin Receptors, Secretory Vesicles, Serotonin, Tryptophan Hydroxylase, Vesicular Biogenic Amine Transport Proteins, Vesicular Monoamine Transport Proteins, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:278
Number:18
Page Range:15850-15858
Date:2 May 2003
Official Publication:https://doi.org/10.1074/jbc.M212816200
PubMed:View item in PubMed

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