Ligand effects on cross-linking support a conformational mechanism for serotonin transport.

ABSTRACT: Serotonin transporter (SERT) is responsible for the re-uptake of 5-hydroxytryptamine (5-HT) from the synaptic cleft after release from serotonergic neurons. We show here that cysteine residues at positions in transmembranes 1 and 3 of SERT, like the corresponding positions in the gamma-aminobutyric acid transporter, can be cross-linked using copper(II)(1,10-phenanthroline)(3). The presence of a cross-link was detected by a novel methionine mutagenesis strategy. A change in mobility for an N-terminal cyanogen bromide fragment accompanied disulfide cross-linking of the two cysteine residues. Cross-linking also inhibited transport, and this process was blocked by cocaine, which is expected to stabilize SERT in conformations where the two positions are separated, but cocaine did not decrease a

SUBMITTER: Tao Z 

PROVIDER: S-EPMC2797150 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature