RGD Reference Report - The first luminal domain of vesicular monoamine transporters mediates G-protein-dependent regulation of transmitter uptake. - Rat Genome Database

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The first luminal domain of vesicular monoamine transporters mediates G-protein-dependent regulation of transmitter uptake.

Authors: Brunk, I  Blex, C  Rachakonda, S  Holtje, M  Winter, S  Pahner, I  Walther, DJ  Ahnert-Hilger, G 
Citation: Brunk I, etal., J Biol Chem. 2006 Nov 3;281(44):33373-85. Epub 2006 Aug 22.
RGD ID: 5130998
Pubmed: PMID:16926160   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M603204200   (Journal Full-text)

The activity of vesicular monoamine transporters (VMATs) is down-regulated by the G-protein alpha-subunits of G(o2) and G(q), but the signaling pathways are not known. We show here that no such regulation is observed when VMAT1 or VMAT2 are expressed in Chinese hamster ovary (CHO) cells. However, when the intracellular compartments of VMAT-expressing CHO cells are preloaded with different monoamines, transport becomes susceptible to G-protein-dependent regulation, with differences between the two transporter isoforms. Epinephrine induces G-protein-mediated inhibition of transmitter uptake in CHOVMAT1 cells but prevents inhibition induced by dopamine in CHOVMAT2 cells. Epinephrine also antagonizes G-protein-mediated inhibition of monoamine uptake by VMAT2 expressing platelets or synaptic vesicles. In CHOVMAT2 cells G-protein-mediated inhibition of monoamine uptake can be induced by 5-hydroxytryptamine (serotonin) 1B receptor agonists, whereas alpha1 receptor agonists modulate uptake into CHOVMAT1 cells. Accordingly, 5-hydroxytryptamine 1B receptor antagonists prevent G-protein-mediated inhibition of uptake in partially filled platelets and synaptic vesicles expressing VMAT2. CHO cells expressing VMAT mutants with a shortened first vesicular loop transport monoamines. However, no or a reduced G-protein regulation of uptake can be initiated. In conclusion, vesicular content is involved in the activation of vesicle associated G-proteins via a structure sensing the luminal monoamine content. The first luminal loop of VMATs may represent a G-protein-coupled receptor that adapts vesicular filling.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc18a2Ratnegative regulation of neurotransmitter transport  IMP  RGD 
Slc18a1Ratnegative regulation of serotonin uptake  IMP G-protein mediated uptake inhibitionRGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc18a1Ratserotonin:sodium:chloride symporter activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc18a1  (solute carrier family 18 member A1)
Slc18a2  (solute carrier family 18 member A2)


Additional Information