RGD Reference Report - Subcellular redistribution of the serotonin transporter by secretory carrier membrane protein 2. - Rat Genome Database

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Subcellular redistribution of the serotonin transporter by secretory carrier membrane protein 2.

Authors: Muller, HK  Wiborg, O  Haase, J 
Citation: Muller HK, etal., J Biol Chem. 2006 Sep 29;281(39):28901-9. Epub 2006 Jul 26.
RGD ID: 4889520
Pubmed: PMID:16870614   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M602848200   (Journal Full-text)

The serotonin transporter (SERT) belongs to the SLC6 family of sodium- and chloride-dependent neurotransmitter transporters responsible for uptake of amino acids and biogenic amines from extracellular spaces. Their activities and subcellular distributions are regulated by various cellular mechanisms, including interactions with other proteins. Using the yeast two-hybrid approach we screened a human brain cDNA library and identified secretory carrier membrane protein 2 (SCAMP2) as a novel SERT-interacting protein. GST-pulldown assays confirmed the physical interaction between SCAMP2 and the N-terminal domain of SERT. In addition, SERT was found to form a complex with SCAMP2 as demonstrated by co-immunoprecipitation from a heterologous expression system and from rat brain homogenate. Co-expression of SERT and SCAMP2 in mammalian cells results in the subcellular redistribution of SERT with a decrease in cell surface SERT and a concomitant reduction in 5-HT uptake activity. Using confocal microscopy we show that in neuronal cells endogenous SERT co-localizes with SCAMP2 in discrete structures also containing the lipid raft marker flotillin-1 and the SNARE protein syntaxin 1A. In contrast, SERT immunoreactivity is clearly segregated from transferrin receptor-containing endosomes. A single amino acid mutation, cysteine-201 to alanine, within the conserved cytoplasmic E peptide of SCAMP2, abolished SCAMP2-mediated down-regulation of SERT, although this mutation had no effect on the physical interaction between SERT and SCAMP2. Taken together, our results suggest that SCAMP2 plays an important role in the regulation of the subcellular distribution of SERT.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
endomembrane system located_inIDA 4889520PMID:16870614UniProt 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Scamp2  (secretory carrier membrane protein 2)
Slc6a4  (solute carrier family 6 member 4)


Additional Information