The Role of Chloride Ions in Serotonin Transport.

ABSTRACT: The human serotonin transporter SERT facilitates serotonin (5-HT⁺) transport into cells by coupling to Na⁺ co-transport and K⁺ exchange. Although extracellular Cl^- is also essential for transport, whether Cl^- ions are transported has been disputed, raising the question why Cl^- ions are required? Here, we examine the role of Cl^- using transport measurements, conformational assays, and molecular simulations. We show that Cl^- is not transported and does not affect Na⁺-mediated cytoplasmic pathway closure but does reduce the accessibility of residues in the extracellular pathway, mimicking transport-related occlusion. Simulations indicate that Cl^- ion binding constrains the helices in

SUBMITTER: Huang J 

PROVIDER: S-EPMC12139788 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature