A salt bridge linking the first intracellular loop with the C terminus facilitates the folding of the serotonin transporter.

ABSTRACT: The folding trajectory of solute carrier 6 (SLC6) family members is of interest because point mutations result in misfolding and thus cause clinically relevant phenotypes in people. Here we examined the contribution of the C terminus in supporting folding of the serotonin transporter (SERT; SLC6A4). Our working hypothesis posited that the amphipathic nature of the C-terminal α-helix (Thr(603)-Thr(613)) was important for folding of SERT. Accordingly, we disrupted the hydrophobic moment of the α-helix by replacing Phe(604), Ile(608), or Ile(612) by Gln. The bulk of the resulting mutants SERT-F604Q, SERT-I608Q, and SERT-I612Q were retained in the endoplasmic reticulum, but their residual delivery to the cell surface still depended on SEC24C. This indicates that the amphipathic nature of the C

SUBMITTER: Koban F 

PROVIDER: S-EPMC4505579 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature