RGD Reference Report - Cysteine-scanning mutagenesis of serotonin transporter intracellular loop 2 suggests an alpha-helical conformation. - Rat Genome Database

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Cysteine-scanning mutagenesis of serotonin transporter intracellular loop 2 suggests an alpha-helical conformation.

Authors: Zhang, YW  Rudnick, G 
Citation: Zhang YW and Rudnick G, J Biol Chem. 2005 Sep 2;280(35):30807-13. Epub 2005 Jul 1.
RGD ID: 1580635
Pubmed: PMID:15994310   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M504087200   (Journal Full-text)

Like other proteins involved in neurotransmitter transport, serotonin transporter (SERT) activity is regulated by multiple intracellular signal transduction pathways. The second intracellular loop (IL2) of SERT contains consensus sequences for cGMP-dependent protein kinase and protein kinase C. A 24-residue region of SERT including IL2, from Ile-270 through Ser-293, was analyzed by cysteine-scanning mutagenesis and chemical modification. 2-(Aminoethyl)methanethiosulfonate hydrobromide (MTSEA) failed to inhibit serotonin transport or binding of the cocaine analog 2beta-carbomethoxy-3beta-(4-[125I]iodophenyl)tropane (beta-CIT) in intact cells expressing these mutants, but it inactivated beta-CIT binding in membrane preparations. From the pattern of sensitivity, IL2 appears to extend from Trp-271 through Ile-290, a significantly longer region than that initially predicted by hydropathy analysis. Six mutants reacted with MTSEA much faster than the others, and the pattern of the more reactive mutations suggested that IL2 is in an alpha-helical conformation. Some of the mutants had significantly elevated transport rates, suggesting a possible mechanism for the regulation of SERT activity.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc6a4Ratserotonin transport  IMP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc6a4Ratcocaine binding  IMP  RGD 
Slc6a4Ratserotonin:sodium:chloride symporter activity  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc6a4  (solute carrier family 6 member 4)


Additional Information